Publications of François JOURET
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See detailSystème rénine-angiotensine-aldostérone:bref historique et questionnements face à la pandémie COVID-19
VALDES SOCIN, Hernan Gonzalo ULiege; JOURET, François ULiege; VROONEN, Laurent ULiege et al

in Revue Médicale de Liège. Supplément (2020), 75

The breakthrough of the secrets of hypertension and the renin-angiotensin-aldosterone system (RAAS) is one of the legends of medicine. The first chapter is the one of Tigerstedt’s experiments about renin ... [more ▼]

The breakthrough of the secrets of hypertension and the renin-angiotensin-aldosterone system (RAAS) is one of the legends of medicine. The first chapter is the one of Tigerstedt’s experiments about renin, and Loesch and Gollblatt’s model of renal hypertension. The race to elucidate the mechanisms of angiotensin, angiotensinogen and the angiotensin conversion enzyme cascade, by Braun Menéndez and Page teams, is a second chapter. The puzzle of this elegant cascade is completed by aldosterone isolation by the collaboration of Tait spouses and Tadeus Rechstein. As a corollary of these findings, Conn made the first description of primary hyperaldosteronism. The elucidation of RAAS pathophysiology naturally led to the synthesis of the antihypertensive captopril by Ondetti and Cushman, thereby opening the modern era of ACE inhibitors and ARII blockers. In March 2020, a viral pandemic caused by SARS-Cov-2 ignites the entire planet. This new coronavirus uses the RAAS angiotensin conversion enzyme type 2 (ACE-2) as a gateway. The SARS-CoV-2/ ACE-2 signalling pathway and its pathological effects on the cardio-respiratory and renal system of these patients initiate a new chapter. The interaction of SARS-Cov-2/ ACE-2 axis with anti-hypertensive agents, as well as with ACE-2 activators and ACE-2 homologs, takes a part of an active international study searching for therapeutic targets. This modern research, summarized in this article, will further develop our knowledge of RAAS and, hopefully, will improve the management of COVID-19 patients. [less ▲]

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See detailMesenchymal Stromal Cells in Solid Organ Transplantation.
VANDERMEULEN, Morgan ULiege; ERPICUM, Pauline ULiege; WEEKERS, Laurent ULiege et al

in Transplantation (2020), 104(5), 923-936

Over the past decade, the clinical application of mesenchymal stromal cells (MSCs) has generated growing enthusiasm as an innovative cell-based approach in solid organ transplantation (SOT). These ... [more ▼]

Over the past decade, the clinical application of mesenchymal stromal cells (MSCs) has generated growing enthusiasm as an innovative cell-based approach in solid organ transplantation (SOT). These expectations arise from a significant number of both transplant- and non-transplant-related experimental studies investigating the complex anti-inflammatory, immunomodulatory and tissue-repair properties of MSCs. Promising preclinical results have prompted clinical trials using MSC-based therapy in SOT. In the present review, the general properties of MSCs are summarized, with a particular emphasis on MSC-mediated impact on the immune system and in the ischemic conditioning strategy. Next, we chronologically detail all clinical trials using MSCs in the field of SOT. Finally, we envision the challenges and perspectives of MSC-based cell therapy in SOT. [less ▲]

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See detailImpact of mesenchymal stroll cells and/or everolimus on T-reg lymphocyte expansion in rats
Vandermeulen, Morgan ULiege; ERPICUM, Pauline ULiege; POMA, Laurence ULiege et al

Conference (2020, March 11)

Background: Mesenchymal stromal cells (MSC) are a promising cell-therapy in solid-organ transplantation, namely because of their immunomodulatory properties and positive impact on the expansion of T ... [more ▼]

Background: Mesenchymal stromal cells (MSC) are a promising cell-therapy in solid-organ transplantation, namely because of their immunomodulatory properties and positive impact on the expansion of T-regulator lymphocytes (Treg). The “optimal” immunosuppressive regimen to be associated with MSC has not been defined. Here, we aimed to evaluate the effects on Treg expansion of a single injection of MSC combined or not with everolimus in rats. Materials and methods: Twenty-four Lewis rats were randomly assigned to 4 groups (n=6 per group): MSC+Evero group, i.e. everolimus (0,25mg/kg/day, SC) from D0 to D14 and iv MSC (±1x106 cells) at D9; MSC group, i.e. placebo from D0 to D14 and iv MSC at D9; Evero group, i.e. everolimus from D0 to D14 and iv saline at D9; control group, i.e. placebo from D0 to D14 and iv saline at D9. T-reg blood levels were measured at D0-14-28 with flow cytometry analysis using anti-CD4,-CD25 and -FoxP3 antibodies. Results: In the two groups infused with MSC, Treg were significantly expanded at D14 and D28 (p<0.01), in comparison to D0. When compared to controls group, the “Evero” group showed a significant expansion of Treg levels at D14 but not at D28. In control, Treg levels did not significantly change compared to D0. Conclusion: A single iv MSC injection was efficient to expand T-reg blood levels. This effect was not altered by everolimus co-administration. Everolimus exposure alone promotes a transient T-reg expansion. Hence, everolimus may be regarded as a co-drug of choice in MSC-based therapy in solid-organ transplantion. [less ▲]

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See detailNouveautés thérapeutiques en Néphrologie : 10 ans d'avancées
BOVY, Christophe ULiege; DELANAYE, Pierre ULiege; JOURET, François ULiege et al

in Revue Médicale de Liège (2020), 75(5-6), 336-343

Chronic kidney disease (CKD) impairs the quality of life and increases the risk for cardiovascular morbimortality. Intensive research is conducted in order to slow down CKD development and progression ... [more ▼]

Chronic kidney disease (CKD) impairs the quality of life and increases the risk for cardiovascular morbimortality. Intensive research is conducted in order to slow down CKD development and progression. During the past decade, a better understanding of the pathophysiological mechanisms of glomerular diseases has highlighted the benefits of rituximab. Progresses have also been made in the understanding of the mechanisms of autosomal polycystic kidney disease, the most frequent inherited kidney disease. These observations led to the discovery and validation of tolvaptan, a blocker of the V2 receptor of the antidiuretic hormone as an innovative treatment. Type 2 diabetic disease is the leading cause worldwide of endstage kidney disease and dialysis. The development of new drugs, such as the gliflozins (inhibiting the sodium glucose reabsorption in the proximal tubule), has contributed to an improvement in the management of the cardiovascular and renal risks especially reducing congestive heart failure rate. Another important progress in nephrology since the beginning of the new century concerns a more precise estimation of the kidney function, which allows to better evaluate the slope of CKD progression and test the influence of different therapeutic approaches aiming at correcting anemia, hyperkalemia, metabolic acidosis and disturbances of calcium and phosphate. The present review summarizes all of these major advances in the field of CKD diagnosis and treatment, and envisions the future of nephrology for the next decade. [less ▲]

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See detailObserver variability in the assessment of renal (18)F-FDG uptake in kidney transplant recipients.
JADOUL, Alexandre ULiege; LOVINFOSSE, Pierre ULiege; BOUQUEGNEAU, Antoine ULiege et al

in Scientific Reports (2020), 10(1), 4617

(18)F-FDG PET/CT imaging may help non-invasively disprove the diagnosis of acute kidney allograft rejection (AR) in kidney transplant recipients (KTR). The present study aims at evaluating the ... [more ▼]

(18)F-FDG PET/CT imaging may help non-invasively disprove the diagnosis of acute kidney allograft rejection (AR) in kidney transplant recipients (KTR). The present study aims at evaluating the repeatability and reproducibility of the quantification of renal (18)F-FDG uptake in KTR. We prospectively performed (18)F-FDG PET/CT in 95 adult KTR who underwent surveillance transplant biopsy between 3 to 6 months post transplantation. Images were obtained 180 minutes after injecting 3 MBq (18)F-FDG per kg body weight. Mean standard uptake value (SUVmean) of kidney cortex was independently measured by 2 experienced observers in 4 volumes of interest (VOI) distributed in the upper (n = 2) and lower (n = 2) poles. The first observer repeated SUV assessment in the uppermost VOI, blinded to the initial results. Intra-class correlation coefficients (ICC) and Bland-Altman plots were calculated. An ICC of 0.96 with 95%CI of [0.94; 0.97] was calculated for the intra-observer measurements. The ICC for inter-observer reproducibility for each VOI was 0.87 [0.81-0.91], 0.87 [0.81-0.91], 0.85 [0.78-0.89] and 0.83 [0.76-0.88] for the upper to the lower renal poles, respectively. The repeatability and reproducibility of the quantification of kidney allograft (18)F-FDG uptake are both consistent, which makes it transferrable to the clinical routine. [less ▲]

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See detailThe use of a visual 4-point scoring scale improves the yield of (18)F-FDG PET-CT imaging in the diagnosis of renal and hepatic cyst infection in patients with autosomal dominant polycystic kidney disease.
Neuville, Marie ULiege; LOVINFOSSE, Pierre ULiege; JADOUL, Alexandre ULiege et al

in European journal of nuclear medicine and molecular imaging (2020)

PURPOSE: [(18)F]FDG PET/CT (PET/CT) proved useful in the diagnosis of renal and hepatic cyst infection (CyI) in patients with autosomal dominant polycystic kidney disease (ADPKD). However, the definition ... [more ▼]

PURPOSE: [(18)F]FDG PET/CT (PET/CT) proved useful in the diagnosis of renal and hepatic cyst infection (CyI) in patients with autosomal dominant polycystic kidney disease (ADPKD). However, the definition of CyI by PET/CT is unclear. Here, we characterize the [(18)F]FDG uptake in CyI in order to infer a visual 4-point diagnostic scale. METHODS: All ADPKD patients hospitalized between 2007 and 2019 for suspected CyI and who underwent an [(18)F]FDG PET/CT scan were listed. CyI was defined by 5 concomitant criteria: fever ≥ 38 °C; abdominal pain; peak plasma CRP ≥ 70 mg/L; no other cause of inflammation; and favorable outcomes after antibiotics for ≥ 21 days. First, all PET/CT images were visually interpreted. Next, the [(18)F]FDG uptake around the suspected CyI was scored using a semiquantitative 4-point scale in comparison to blood and liver activities. RESULTS: Sixty [(18)F]FDG PET/CT scans were performed for suspected CyI in 38 ADPKD patients. Twenty-nine episodes met the gold-standard criteria for CyI. The visual assessment of PET/CT images reached a sensitivity of 73.1% and a specificity of 70.6%. Using the 4-point scale, an [(18)F]FDG score ≥ 3 (i.e., cyst uptake > liver) improved the specificity to 85.3%. CONCLUSION: [(18)F]FDG PET-CT is helpful in CyI diagnosis in ADPKD, and the use of a 4-point scoring of [(18)F]FDG uptake improves its diagnostic yield, with positive and negative predictive values of 78.3 and 78.4%, respectively. External validation is required. [less ▲]

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See detailMechanisms involved in AMPK-mediated deposition of tight junction components to the plasma membrane.
Wu, Jingshing; Rowart, Pascal; Jouret, François ULiege et al

in American journal of physiology. Cell physiology (2020)

AMP activated protein kinase (AMPK) activation promotes early stages of epithelial junction assembly. AMPK activation in MDCK renal epithelial cells facilitates localization of the junction-associated ... [more ▼]

AMP activated protein kinase (AMPK) activation promotes early stages of epithelial junction assembly. AMPK activation in MDCK renal epithelial cells facilitates localization of the junction-associated proteins aPKCzeta and Par3 to the plasma membrane and promotes conversion of Cdc42, a key regulator of epithelial polarization and junction assembly, to its active GTP bound state. Furthermore, Par3 is an important regulator of AMPK-mediated aPKCzeta localization. Both aPKCzeta and Par3 serve as intermediates in AMPK-mediated junction assembly, with inhibition of aPKCzeta activity or Par3 knockdown disrupting AMPK's ability to facilitate zonula occludens (ZO-1) localization. AMPK phosphorylates the adherens junction protein afadin and regulates its interaction with the tight junction protein zonula occludens (ZO)-1. Afadin is phosphorylated at two critical sites, S182 (residing within an aPKCzeta consensus site) and S1049 (residing within an AMPK consensus site), that are differentially regulated during junction assembly and that exert different effects on the process. Expression of phospho-defective mutants (S182A and S1082A) perturbed ZO-1 localization to the plasma membrane during AMPK-induced junction assembly. Expression of S182A increased the ZO-1/afadin interaction, while S1049A reduced this interaction during extracellular calcium-induced junction assembly. Inhibition of aPKCzeta activity also increased the ZO-1/afadin interaction. Taken together, these data suggest that aPKCzeta phosphorylation of afadin terminates the ZO-1/afadin interaction, and thus permits the later stages of junction assembly. [less ▲]

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See detailImplications of early diagnosis of autosomal dominant polycystic kidney disease: A post hoc analysis of the TEMPO 3:4 trial.
Janssens, Peter; Jouret, François ULiege; Bammens, Bert et al

in Scientific Reports (2020), 10(1), 4294

It is unknown whether early diagnosis of autosomal dominant polycystic kidney disease (ADPKD) can enable earlier management and improve outcomes. We conducted a post hoc analysis of data from the TEMPO 3 ... [more ▼]

It is unknown whether early diagnosis of autosomal dominant polycystic kidney disease (ADPKD) can enable earlier management and improve outcomes. We conducted a post hoc analysis of data from the TEMPO 3:4 trial. Subjects were stratified by ADPKD diagnosis at age </=18 (childhood diagnosis [CD]) or>18 (adulthood diagnosis [AD]). Groups were compared for baseline characteristics and total kidney volume (TKV) growth and estimated glomerular filtration rate (eGFR) decline over 3 years. 294 CD and 1148 AD subjects were analyzed. At inclusion, CD subjects were younger (mean age 34.2 versus 39.8 years; p < 0.0001) and had better eGFR (mean +/- SD 87.4 +/- 23.9 versus 80.1 +/- 20.7 mL/min/1.73 m(2); p < 0.0001), while CD had more severe Mayo risk classification (p < 0.0001) and more PKD1 mutations (p = 0.003). No statistical differences were found in TKV or eGFR change. At study end, placebo-treated CD subjects had better eGFR than projected by a prediction equation (mean difference +/-SD for observed versus predicted eGFR: 2.18 +/- 10.7 mL/min/1.73 m(2); p = 0.0475). However, these results are not confirmed when excluding stage 1 CKD. Whether CD subjects, despite their risk profile, have a slower disease course than predicted remains inconclusive. Future studies are needed to confirm that early diagnosis and management can alter the disease course of ADPKD. [less ▲]

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See detailLa radiothérapie centrée sur le rein atténue les lésions d'ischémie-reperfusion rénale chez la souris
Khbouz, Badr ULiege; Pascal, Rowart; LALLEMAND, François ULiege et al

Conference (2019, December 04)

Introduction: L'irradiation corporelle engendre un conditionnement ischémique rénal. L’impact fonctionnel et pathophysiologique d’une radiothérapie centrée sur les reins est cependant inconnu. Méthodes ... [more ▼]

Introduction: L'irradiation corporelle engendre un conditionnement ischémique rénal. L’impact fonctionnel et pathophysiologique d’une radiothérapie centrée sur les reins est cependant inconnu. Méthodes: Expérience 1: Sous anesthésie, 2 faisceaux de rayons X (225Kv, 13mA) ciblent spécifiquement les reins pour une dose totale de 8,56Gy. Trente jours plus tard, une néphrectomie droite est réalisée et une ischémie du rein gauche est induite pendant 30min. Après 48h de reperfusion, le rein gauche et le sang sont prélevés (n=6 souris). Un groupe témoin (n=6) subit une I/R rénale similaire sans irradiation préalable. Expérience 2: Une irradiation unilatérale des reins gauches (8,56Gy) est réalisée (n=11). Trente jours plus tard, le rein gauche est prélevé. Le rein gauche de souris non irradiées (n=5) est utilisé comme contrôle. L’ARN des reins irradiés et contrôles est extrait pour une transcriptomique comparative (BaseSpace Illumina; DAVID program). Résultats: À la suite d’une I/R rénale, le taux d’urée était significativement plus bas chez les animaux pré-irradiées (148±93mg/dl), comparativement aux contrôles (496±33, p<0,01). Le nombre de cellules en prolifération (PCNA-positives) était significativement inférieur chez les pré-irradiées par rapport aux témoins (131±53 vs. 545±257/mm², p<0,001). L'infiltration rénale par les cellules CD11b-positives (90±32 vs. 414±149/mm²) et les macrophages F4-80 (81±23 vs 179±68/mm²) était significativement réduite dans le groupe irradié. L’analyse transcriptomique montre une up-régulation des voies de signalisation de l'angiogenèse (Hmox1) et de la réponse au stress (Hspa1a, Hspa1b), et une down-régulation de l'oxydoréduction (Nox4). Conclusion: L'irradiation rénale induit un pré-conditionnement ischémique chez la souris, avec une fonction rénale préservée et une inflammation atténuée après I/R rénale. Les voies de signalisation susmentionnées, modulées lors de l’irradiation, participent probablement à la résistance du rein à l'I/R. [less ▲]

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See detailKidney targeted radiotherapy attenuates the renal ischemia-reperfusion injury in mice
Khbouz, Badr ULiege; Rowart, Pascal; LALLEMAND, François ULiege et al

Poster (2019, November 07)

BACKGROUND Whole-body irradiation has been associated with renal ischemic preconditioning in mice. Here, we investigate the functional and fundamental impact of radiotherapy centered on the kidneys before ... [more ▼]

BACKGROUND Whole-body irradiation has been associated with renal ischemic preconditioning in mice. Here, we investigate the functional and fundamental impact of radiotherapy centered on the kidneys before renal ischemia/reperfusion (I/R) in mice. METHODS Experience1: Animals (n=6) were anesthetized and placed in the irradiator. Two beams of X-rays (225Kv, 13 mA) specifically targeted both kidneys to deliver a dose a 8,56Gy. One month later, a right nephrectomy was performed, and a left renal ischemia was induced for 30min. After 48 hours of reperfusion, the left kidney was collected, as well as blood. Control group (n=6) underwent a similar renal I/R procedure, with no prior irradiation. Experience 2: Unilateral irradiation of the left kidney (8.56 Gy) was performed in mice (n=10). One month later, the left (irradiated) kidney was collected. Additionally, the left kidneys were collected from non-irradiated mice (n=5). Total RNAs were extracted from irradiated and control kidneys to perform comparative high-throughput RNA-Seq. BaseSpace Sequence Hub Illumina was used. Functional enrichment analysis was performed using DAVID program. Both experimental protocols have been approved by the IACUC of ULiège, Liège, Belgium. RESULTS Following kidney I/R, blood urea nitrogen (BUN) levels were significantly lower in pre-irradiated mice (148.4±93.1) compared to controls (495.7±33.3, p<0.01). The number of PCNA-positive proliferating cells was significantly lower in pre-irradiated mice (130.8±52.7) compared to controls (545.4±257.3, p<0.001). The renal infiltration by inflammatory CD11b-positive cells (90.2±32.2 vs. 414.5±148.6) and F4-80-positive macrophages (80.6±22.9 vs. 178.5±68) was significantly reduced in pre-irradiated animals vs. controls. Comparative transcriptomics showed a significant up-regulation of various signaling pathways, including angiogenesis (HMOX1) and stress response (HSPA1A, HSPA1B), and a down-regulation of oxidoreduction (NOX4). CONCLUSION Kidney irradiation induces ischemic preconditioning in mice, with improved renal function and decreased inflammation following renal I/R. The aforementioned signaling pathways may play a role in irradiation-associated kidney resistance to I/R. [less ▲]

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See detailKidney-centered radiotherapy attenuates renal ischemia-reperfusion injury in mice
Khbouz, Badr ULiege; Rowart, Pascal ULiege; LALLEMAND, François ULiege et al

Conference (2019, October 11)

Introduction Whole-body irradiation has been associated with renal ischemic preconditioning in mice. Here, we investigate the functional and fundamental impact of radiotherapy centered on the kidneys ... [more ▼]

Introduction Whole-body irradiation has been associated with renal ischemic preconditioning in mice. Here, we investigate the functional and fundamental impact of radiotherapy centered on the kidneys before renal ischemia/reperfusion (I/R) in mice. Materials and Methods Experience1: Animals (n=5) were anesthetized and placed in the irradiator. Two beams of X-rays (225Kv, 13 mA) specifically targeted both kidneys to delivered a dose of 8,56Gy. One month later, a right nephrectomy was performed, and a left renal ischemia was induced for 30min. After 48 hours of reperfusion, the left kidney was collected, as well as blood. Control group (n=6) underwent a similar renal I/R procedure, with no prior irradiation. Experience 2: Unilateral irradiation of left kidneys (8.56 Gy) was performed on mice (N=11). One month later, the left (irradiated) kidney was collected. Additionally, kidneys were collected from non-irradiated mice (N=5). Total RNAs were extracted from irradiated and control kidneys to perform comparative high-throughput RNA-Seq. BaseSpace Sequence Hub Illumina was used. Functional enrichment analysis was performed using DAVID program. Results Following kidney I/R, blood urea nitrogen (BUN) levels were significantly lower in pre-irradiated mice (148.4±93.1) compared to controls (495.7±33.3, p<0.01). The number of PCNA-positive proliferating cells was significantly lower in pre-irradiated mice (130.8±52.7) compared to controls (545.4±257.3, p<0.001). The renal infiltration by inflammatory CD11b-positive cells (90.2±32.2) vs. (414.5±148.6) and F4-80-positive macrophages (80.6±22.9) vs. (178.5±68) was significantly reduced in pre-irradiated animals. Comparative transcriptomics showed a significant up-regulation of signaling pathways involved in angiogenesis (HMOX1) and stress response (HSPA1A, HSPA1B), and a down-regulation of oxidoreduction (NOX4). Conclusion Kidney irradiation induces ischemic preconditioning in mice, with improved renal function and decreased inflammation following renal I/R. The aforementioned signaling pathways may play a role in irradiation-associated kidney resistance to I/R. [less ▲]

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See detailGut Microbiota and Fecal Levels of Short-Chain Fatty Acids Differ Upon 24-Hour Blood Pressure Levels in Men
Huart, Justine ULiege; Leenders, Justine ULiege; Taminiau, Bernard ULiege et al

in Hypertension (2019)

Gut microbiota may influence blood pressure (BP), namely via end products of carbohydrate fermentation. After informed consent, male volunteers were prospectively categorized into 3 groups upon European ... [more ▼]

Gut microbiota may influence blood pressure (BP), namely via end products of carbohydrate fermentation. After informed consent, male volunteers were prospectively categorized into 3 groups upon European Society of Hypertension criteria based on 24-hour ambulatory BP measurements: (1) hypertension, (2) borderline hypertension, and (3) normotension. Stool, urine and serum samples were collected in fasting conditions. Gut microbiota was characterized by 16S amplicon sequencing. Metabolomics, including quantification of short-chain fatty acids, was conducted using nuclear magnetic resonance. Two-way ANOVA combined with Tukey post hoc test, as well as multiple permutation test and Benjamini-Hochberg-Yekutieli false discovery rate procedure, was used. The cohort included 54 males: 38 hypertensive (including 21 under treatment), 7 borderline, and 9 normotensive. No significant difference was observed between groups concerning age, body mass index, smoking habits, and weekly alcohol consumption. The genus Clostridium sensu stricto 1 positively correlated with BP levels in nontreated patients (n=33). This correlation was significant after multiple permutation tests but was not substantiated following false discovery rate adjustment. Short-chain fatty acid levels were significantly different among groups, with higher stool levels of acetate, butyrate, and propionate in hypertensive versus normotensive individuals. No difference was observed in serum and urine metabolomes. Correlation between stool metabolome and 24-hour BP levels was evidenced, with R2 reaching 0.9. Our pilot study based on 24-hour ambulatory BP measurements, 16S amplicon sequencing, and metabolomics supports an association between gut microbiota and BP homeostasis, with changes in stool abundance of short-chain fatty acids. [less ▲]

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See detail"Acute kidney dysfunction with no rejection" is associated with poor renal outcomes at 2 years post kidney transplantation.
PAQUOT, Francois ULiege; WEEKERS, Laurent ULiege; BONVOISIN, Catherine ULiege et al

in BMC Nephrology (2019), 20(1), 249

BACKGROUND: "Acute kidney dysfunction with no rejection" (ADNR) corresponds to acute kidney injury without histological evidence of acute rejection (AR) in kidney transplant recipients (KTR). The ... [more ▼]

BACKGROUND: "Acute kidney dysfunction with no rejection" (ADNR) corresponds to acute kidney injury without histological evidence of acute rejection (AR) in kidney transplant recipients (KTR). The prognosis of ADNR is unknown. METHODS: From 2007 to 2015, we categorized KTR with for-cause kidney biopsy within the first 12 months post kidney transplantation (KTx) into ADNR (n = 93) and biopsy-proven AR (n = 22). Controls (C, n = 135) included KTR with no ADNR or AR within the first 24 months post-KTx. A piecewise linear regression with a single fixed-knot at 12 months served to establish intercepts and slopes of MDRD-eGFR variations from 12 to 24 months. The percentage of KTR with >/=30% reduction of eGFR from 12 to 24 months was calculated as a surrogate marker of future graft loss. RESULTS: The median time for for-cause biopsy was 22 [10-70] and 13 [7-43] days for ADNR and AR, respectively. At 12 months, eGFR was significantly higher in C (57.6 +/- 14.9 mL/min/1.73m(2)) vs. ADNR (43.5 +/- 15.4 mL/min/1.73m(2), p < 0.0001) and vs. AR (46.5 +/- 15.2 mL/min/1.73m(2), p < 0.0065). The proportion of KTR with >/=30% reduction in eGFR from 12 to 24 months reached 16.3% in C vs. 29.9% in ADNR (p = 0.02) and vs. 15% in AR (not significant). CONCLUSIONS: ADNR is associated with poor outcomes within 2 years post-KTx. [less ▲]

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See detailDiagnostic différentiel des kystes rénaux : importance de l'approche génétique
GHUYSEN, Camille ULiege; Neuville, Marie ULiege; KRZESINSKI, Jean-Marie ULiege et al

in Revue Médicale de Liège (2019), 74(11), 580-585

The incidental finding of renal cysts is a common clinical situation given their high prevalence (~ 50 % after the age of 50) and the continuous improvement of abdomen imaging. Diagnosis is central to ... [more ▼]

The incidental finding of renal cysts is a common clinical situation given their high prevalence (~ 50 % after the age of 50) and the continuous improvement of abdomen imaging. Diagnosis is central to appropriately dictate the management of the patient. During the diagnostic work-up, it is important to consider (i) the aspect of the cysts, (ii) their number, (iii) and their location, as well as (iv) the age of the patient and his/her personal and familial medical history, (v) the presence of extra-renal manifestations, (vi) and the renal function (including the urinary sediment). Starting from an atypical clinical case characterized by a rapidly evolving chronic kidney disease associated with bilateral renal cysts, we review the classical diagnostic work-up of kidney cysts. As a conclusion, we propose a diagnostic algorithm including both acquired and hereditary nephropathies. [less ▲]

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See detailLa tomographie par emission de positons au 18F-FDG en pathologie renale non oncologique : indications actuelles et perspectives.
HANSSEN, Oriane ULiege; LOVINFOSSE, Pierre ULiege; WEEKERS, Laurent ULiege et al

in Nephrologie & therapeutique (2019)

Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which provides anatomical and functional information. PET/CT is increasingly used in non-oncological ... [more ▼]

Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which provides anatomical and functional information. PET/CT is increasingly used in non-oncological nephrology since conventional radiological approaches after injection of contrast agents are relatively contra-indicated in patients with chronic kidney disease (CKD). PET/CT after i.v. injection of (18)F-fluoro-deoxy-glucose (FDG) is not toxic and is characterized by a high sensitivity. The level of irradiation ( approximately 5mSv) is acceptable. CKD does not significantly influence tissue uptake of (18)F-FDG. The purpose of the present review aims at detailing the non-oncological indications of (18)F-FDG PET/CT in general nephrology and after kidney transplantation. Particularly, (18)F-FDG PET/CT appears useful in the diagnosis of cyst infection in patients with autosomal dominant polycystic kidney disease, as well as in the characterization of retroperitoneal fibrosis. In kidney transplant recipients, (18)F-FDG PET/CT may help in the diagnostic work-up of suspected acute rejection, thereby eventually avoiding unnecessary kidney transplant biopsy. Perspectives in (18)F-FDG PET/CT imaging are discussed, including innovative approaches of image analysis. [less ▲]

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See detailOxidative stress in chronic kidney disease
Daenen, K.; Andries, A.; Mekahli, D. et al

in Pediatric Nephrology: Journal of the International Pediatric Nephrology Association (2019)

Oxidative stress (OS), defined as disturbances in the pro-/antioxidant balance, is harmful to cells due to the excessive generation of highly reactive oxygen (ROS) and nitrogen (RNS) species. When the ... [more ▼]

Oxidative stress (OS), defined as disturbances in the pro-/antioxidant balance, is harmful to cells due to the excessive generation of highly reactive oxygen (ROS) and nitrogen (RNS) species. When the balance is not disturbed, OS has a role in physiological adaptations and signal transduction. However, an excessive amount of ROS and RNS results in the oxidation of biological molecules such as lipids, proteins, and DNA. Oxidative stress has been reported in kidney disease, due to both antioxidant depletions as well as increased ROS production. The kidney is a highly metabolic organ, rich in oxidation reactions in mitochondria, which makes it vulnerable to damage caused by OS, and several studies have shown that OS can accelerate kidney disease progression. Also, in patients at advanced stages of chronic kidney disease (CKD), increased OS is associated with complications such as hypertension, atherosclerosis, inflammation, and anemia. In this review, we aim to describe OS and its influence on CKD progression and its complications. We also discuss the potential role of various antioxidants and pharmacological agents, which may represent potential therapeutic targets to reduce OS in both pediatric and adult CKD patients. © 2018, IPNA. [less ▲]

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See detailOxidative stress in autosomal dominant polycystic kidney disease: player and/or early predictor for disease progression?
Andries, Asmin; Daenen, Kristien; Jouret, François ULiege et al

in Pediatric Nephrology: Journal of the International Pediatric Nephrology Association (2019)

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in PKD1 or PKD2 genes, is the most common hereditary renal disease. Renal manifestations of ADPKD are gradual cyst development and ... [more ▼]

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in PKD1 or PKD2 genes, is the most common hereditary renal disease. Renal manifestations of ADPKD are gradual cyst development and kidney enlargement ultimately leading to end-stage renal disease. ADPKD also causes extrarenal manifestations, including endothelial dysfunction and hypertension. Both of these complications are linked with reduced nitric oxide levels related to excessive oxidative stress (OS). OS, defined as disturbances in the prooxidant/antioxidant balance, is harmful to cells due to the excessive generation of highly reactive oxygen and nitrogen free radicals. Next to endothelial dysfunction and hypertension, there is cumulative evidence that OS occurs in the early stages of ADPKD. In the current review, we aim to summarize the cardiovascular complications and the relevance of OS in ADPKD and, more specifically, in the early stages of the disease. First, we will briefly introduce the link between ADPKD and the early cardiovascular complications including hypertension. Secondly, we will describe the potential role of OS in the early stages of ADPKD and its possible importance beyond the chronic kidney disease (CKD) effect. Finally, we will discuss some pharmacological agents capable of reducing reactive oxygen species and OS, which might represent potential treatment targets for ADPKD. [less ▲]

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See detailInfusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study.
ERPICUM, Pauline ULiege; WEEKERS, Laurent ULiege; DETRY, Olivier ULiege et al

in Kidney International (2019), 95

Mesenchymal stromal cells (MSCs) exhibit anti-inflammatory and immune-regulatory properties, and preclinical studies suggest a potential benefit in solid organ transplantation. We report on the 1-year ... [more ▼]

Mesenchymal stromal cells (MSCs) exhibit anti-inflammatory and immune-regulatory properties, and preclinical studies suggest a potential benefit in solid organ transplantation. We report on the 1-year follow-up of an open-label phase I-II trial of a single infusion of third-party MSC post-kidney transplantation, in addition to standard immunosuppression. Ten kidney transplant recipients from deceased donors received third-party bone marrow MSCs ( approximately 2 x 10(6)/kg) on day 3 +/- 2 post-transplant and were compared to 10 concurrent controls. No adverse effects were noted at MSC injection. One participant with a history of cardiac disease had a non-ST-elevation myocardial infarction approximately 3 hours after MSC infusion. Incidences of opportunistic infections and acute rejection were similar. At day 7 post-transplant, estimated glomerular filtration rate (eGFR) in MSC-treated recipients reached 48.6 ml/min/1.73m(2), compared to 32.5 ml/min/1.73m(2)in controls and 29.3 ml/min/1.73m(2)in our overall cohort of kidney transplant recipients. No difference in eGFR was found at 1 year. MSC-treated recipients showed increased frequencies of regulatory T cells at day 30, with no significant change in B cell frequencies compared to concurrent controls. Four MSC-treated participants developed antibodies against MSC or shared kidney-MSC HLA, with only 1 with MFI >1500. A single infusion of third-party MSC following kidney transplantation appears to be safe, with one cardiac event of unclear relationship to the intervention. MSC therapy is associated with increased regulatory T cell proportion and with improved early allograft function. Long-term effects, including potential immunization against MSC, remain to be studied. [less ▲]

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