References of "JOURET, François"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailCinacalcet treatment at the time of transplantation is associated with a significant risk of delayed graft function in kidney transplant recipients
Jouret, François ULg; WEEKERS, Laurent ULg; GROSCH, Stéphanie ULg et al

in Transplant International (2014, May), 27(S1), 167

The calcium-sensing receptor (CaSR) has been implicated in the ischemia/ reperfusion (I/R) cascade in heart, liver and brain. Renal I/R occurs at the time of transplantation (Tx), with a deleterious ... [more ▼]

The calcium-sensing receptor (CaSR) has been implicated in the ischemia/ reperfusion (I/R) cascade in heart, liver and brain. Renal I/R occurs at the time of transplantation (Tx), with a deleterious impact on early graft function. Here, we retrospectively investigated if the use of cinacalcet, a CaSR agonist, in kidney transplant recipients (KTR) influences early graft recovery. All KTR from 2007 to 2012 in our Academic Hospital were prospectively included in a database. Patients actively treated with cinacalcet on the day of Tx were retrospectively identified from this database and matched with controls on (i) type of donor (living [LD], deceased after brain or circulatory death [DCD]); (ii) cold ischemic time (CIT) ` 1 h; (iii) residual diuresis (` 500 ml); and (iv) donor age (` 5 years). Delayed graft function (DGF) was defined as dialysis requirement after Tx. Baseline characteristics were compared between groups with student’s t-test or Chi-2 as appropriate. The endpoint was the percentage of DGF in both groups. Among 337 KTR, 36 (10.7%) were treated with cinacalcet at Tx. Control group included 61 patients. Characteristics of patients and donors are summarized in the table. DGF occurred in 42 and 23% of cinacalcet-treated and control groups, respectively (p = 0.05). These retro- spective observations suggest that CaSR activation at the time of Tx impairs early graft recovery. [less ▲]

Detailed reference viewed: 27 (13 ULg)
Full Text
Peer Reviewed
See detailTwo novel mutations of the CLDN16 gene cause familial hypomagnesaemia with hypercalciuria and nephrocalcinosis
Hanssen, Oriane ULg; CASTERMANS, Emilie ULg; BOVY, Christophe ULg et al

in Clinical Kidney Journal (2014), 7

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is an autosomal-recessive disease caused by mutations in the CLDN16 or CLDN19 genes, which encode tight junction-associated proteins ... [more ▼]

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is an autosomal-recessive disease caused by mutations in the CLDN16 or CLDN19 genes, which encode tight junction-associated proteins, claudin-16 and -19. The resultant tubulopathy leads to urinary loss of Mg2+ and Ca2+, with subsequent nephrocalcinosis and end-stage renal disease (ESRD). An 18-year-old boy presented with chronic kidney disease and proteinuria, as well as hypomagnesaemia, hypercalciuria and nephrocalcinosis. A kidney biopsy revealed tubular atrophy, interstitial fibrosis and segmental sclerosis of some glomeruli. Two novel mutations in the CLDN16 gene were identified: c.340C>T (nonsense) and c.427+5G>A (splice site). The patient reached ESRD at 23 and benefited from kidney transplantation. [less ▲]

Detailed reference viewed: 10 (7 ULg)
Full Text
Peer Reviewed
See detailMesenchymal stromal cell therapy in conditions of renal ischaemia/reperfusion.
Erpicum, Pauline; Detry, Olivier; Weekers, Laurent et al

in Nephrology Dialysis Transplantation (2014)

Acute kidney injury (AKI) represents a worldwide public health issue of increasing incidence, with a significant morbi-mortality. AKI treatment mostly relies on supportive manoeuvres in the absence of ... [more ▼]

Acute kidney injury (AKI) represents a worldwide public health issue of increasing incidence, with a significant morbi-mortality. AKI treatment mostly relies on supportive manoeuvres in the absence of specific target-oriented therapy. The pathophysiology of AKI commonly involves ischaemia/reperfusion (I/R) events, which cause both immune and metabolic consequences in renal tissue. Similarly, at the time of kidney transplantation (KT), I/R is an unavoidable event which contributes to early graft dysfunction and enhanced graft immunogenicity. Mesenchymal stromal cells (MSCs) represent a heterogeneous population of adult, fibroblast-like multi-potent cells characterized by their ability to differentiate into tissues of mesodermal lineages. Because MSC have demonstrated immunomodulatory, anti-inflammatory and tissue repair properties, MSC administration at the time of I/R and/or at later times has been hypothesized to attenuate AKI severity and to accelerate the regeneration process. Furthermore, MSC in KT could help prevent both I/R injury and acute rejection, thereby increasing graft function and survival. In this review, summarizing the encouraging observations in animal models and in pilot clinical trials, we outline the benefit of MSC therapy in AKI and KT, and envisage their putative role in renal ischaemic conditioning. [less ▲]

Detailed reference viewed: 22 (9 ULg)
Full Text
Peer Reviewed
See detailParathormone and bone-specific alkaline phosphatase for the follow-up of bone turnover in hemodialysis patients : Is it so simple?
DELANAYE, Pierre ULg; DUBOIS, Bernard ULg; JOURET, François ULg et al

in Clinica Chimica Acta (2013), 417

Background: Chronic Kidney Disease (CKD) is associated with mineral and bone disorders (MBD). International guidelines suggest that levels of serum parathormone (PTH) or bone-specific alkaline phosphatase ... [more ▼]

Background: Chronic Kidney Disease (CKD) is associated with mineral and bone disorders (MBD). International guidelines suggest that levels of serum parathormone (PTH) or bone-specific alkaline phosphatase (b-ALP) can be used to evaluate MBD in dialysis patients. The evidence remains moderate and based on transversal studies. <br />Methods: We retrospectively investigated the variations of PTH (ΔPTH) and b-ALP (Δb-ALP) serum concentrations over a short (6-weeks) and a long (one-year) period in a monocentric hemodialysis population. The proportion of patients reaching the critical difference (CD) (50% for PTH and 25% for b-ALP) was calculated. <br />Results: Seventy-seven patientswere included. A significant correlation between PTHand b-ALP levelswas found at baseline (r=0.51). By contrast, no correlation was observed between ΔPTH and Δb-ALP over a 6-week interval (r=0.07). The CD for PTH and b-ALP was reached by 19 and 11 patients, respectively, with 2 patients showing consistent variations of both biomarkers. One year later, measurements were repeated in 48 survivors. <br />No correlation was found between ΔPTH and Δb-ALP (r=0.27). The CD for PTH or b-ALP was reached by 24 patients and 28 patients, respectively, with 6 patients (12.5%) showing opposite results for both biomarkers. <br />Conclusion: This study shows the lack of correlation between ΔPTH and Δb-ALP over time in patients under chronic hemodialysis. [less ▲]

Detailed reference viewed: 42 (17 ULg)
Full Text
Peer Reviewed
See detailPlace de l'AMP-activated protein kinase dans le preconditionnement ischemique renal.
Erpicum, Pauline; Krzesinski, Jean-Marie ULg; Jouret, François ULg

in Nephrologie & therapeutique (2013)

Kidney transplantation represents the best treatment of end-stage renal disease. In addition to the degree of human leukocyte antigen matching, long-term graft survival is influenced by the quality of the ... [more ▼]

Kidney transplantation represents the best treatment of end-stage renal disease. In addition to the degree of human leukocyte antigen matching, long-term graft survival is influenced by the quality of the graft before its transplantation. Quality criteria include the level of ischemic damage caused by the transplantation per se. Renal ischemic preconditioning (IP) consists of different approaches to prevent ischemia/reperfusion (I/R) damage induced by the interruption and recovery of renal circulation, as observed during transplantation. Distinct animal models show promising results regarding the efficiency of PCI to preserve kidney structure and function in I/R conditions. Characterizing the cellular cascades involved in I/R led to the identification of putative targets of renal IP, including the adenosine monophosphate-activated protein kinase (AMPK). AMPK is a ubiquitous energy sensor, which has been implicated in the maintenance of epithelial cell polarization under energy deprivation. Among others, the anti-diabetic drug, metformin, is a potent activator of AMPK. Here, we summarize the in vitro and in vivo data about the role of AMPK in renal IP. Defining the pharmacological conditions of IP would help to improve the quality of the renal graft before its transplantation, thereby increasing its long-term survival. [less ▲]

Detailed reference viewed: 21 (7 ULg)
Full Text
Peer Reviewed
See detailActivation of the Ca(2)+-sensing receptor induces deposition of tight junction components to the epithelial cell plasma membrane.
Jouret, François ULg; Wu, Jingshing; Hull, Michael et al

in Journal of cell science (2013), 126(Pt 22), 5132-42

The Ca(2+)-sensing receptor (CaSR) belongs to the G-protein-coupled receptor superfamily and plays essential roles in divalent ion homeostasis and cell differentiation. Because extracellular Ca(2+) is ... [more ▼]

The Ca(2+)-sensing receptor (CaSR) belongs to the G-protein-coupled receptor superfamily and plays essential roles in divalent ion homeostasis and cell differentiation. Because extracellular Ca(2+) is essential for the development of stable epithelial tight junctions (TJs), we hypothesized that the CaSR participates in regulating TJ assembly. We first assessed the expression of the CaSR in Madin-Darby canine kidney (MDCK) cells at steady state and following manipulations that modulate TJ assembly. Next, we examined the effects of CaSR agonists and antagonists on TJ assembly. Immunofluorescence studies indicate that endogenous CaSR is located at the basolateral pole of MDCK cells. Stable transfection of human CaSR in MDCK cells further reveals that this protein co-distributes with beta-catenin on the basolateral membrane. Switching MDCK cells from low-Ca(2+) medium to medium containing a normal Ca(2+) concentration significantly increases CaSR expression at both the mRNA and protein levels. Exposure of MDCK cells maintained in low-Ca(2+) conditions to the CaSR agonists neomycin, Gd(3+) or R-568 causes the transient relocation of the tight junction components ZO-1 and occludin to sites of cell-cell contact, while inducing no significant changes in the expression of mRNAs encoding junction-associated proteins. Stimulation of CaSR also increases the interaction between ZO-1 and the F-actin-binding protein I-afadin. This effect does not involve activation of the AMP-activated protein kinase. By contrast, CaSR inhibition by NPS-2143 significantly decreases interaction of ZO-1 with I-afadin and reduces deposition of ZO-1 at the cell surface following a Ca(2+) switch from 5 microM to 200 microM [Ca(2+)]e. Pre-exposure of MDCK cells to the cell-permeant Ca(2+) chelator BAPTA-AM, similarly prevents TJ assembly caused by CaSR activation. Finally, stable transfection of MDCK cells with a cDNA encoding a human disease-associated gain-of-function mutant form of the CaSR increases the transepithelial electrical resistance of these cells in comparison to expression of the wild-type human CaSR. These observations suggest that the CaSR participates in regulating TJ assembly. [less ▲]

Detailed reference viewed: 6 (1 ULg)
Full Text
Peer Reviewed
See detailTolvaptan in autosomal dominant polycystic kidney disease.
JOURET, François ULg; Krzesinski, Jean-Marie ULg

in New England Journal of Medicine [=NEJM] (2013), 368(13), 1258-9

Detailed reference viewed: 43 (6 ULg)
Full Text
Peer Reviewed
See detailClostridium perfringens hip arthritis in a haemodialysis patient.
Ho, T. T.; Labriola, L.; JOURET, François ULg et al

in Acta Clinica Belgica (2012), 67(1), 49-50

Haemodialysis patients have acquired immunity disturbances, co-morbidities and a vascular access, factors predisposing them to infection and bacteraemia. Clostridium perfringens is an anaerobic bacterium ... [more ▼]

Haemodialysis patients have acquired immunity disturbances, co-morbidities and a vascular access, factors predisposing them to infection and bacteraemia. Clostridium perfringens is an anaerobic bacterium potentially causing severe infections, including rarely septic arthritis. We report the first case of Clostridium perfringens septic arthritis in a haemodialysis patient and suggest a haematogenous spread. After rapid joint lavage combined with appropriate anti-microbial therapy, the patient recovered. [less ▲]

Detailed reference viewed: 12 (0 ULg)
Full Text
Peer Reviewed
See detailDiagnosis of cyst infection in patients with autosomal dominant polycystic kidney disease: attributes and limitations of the current modalities.
JOURET, François ULg; Lhommel, Renaud; Devuyst, Olivier et al

in Nephrology Dialysis Transplantation (2012), 27(10), 3746-51

Cyst infection is a diagnostic challenge in patients with autosomal dominant polycystic kidney disease (ADPKD) because of the lack of specific manifestations and limitations of conventional imaging ... [more ▼]

Cyst infection is a diagnostic challenge in patients with autosomal dominant polycystic kidney disease (ADPKD) because of the lack of specific manifestations and limitations of conventional imaging procedures. Still, recent clinical observations and series have highlighted common criteria for this condition. Cyst infection is diagnosed if confirmed by cyst fluid analysis showing bacteria and neutrophils, and as a probable diagnosis if all four of the following criteria are concomitantly met: temperature of >38 degrees C for >3 days, loin or liver tenderness, C-reactive protein plasma level of >5 mg/dL and no evidence for intracystic bleeding on computed tomography (CT). In addition, the elevation of serum carbohydrate antigen 19-9 (CA19-9) has been proposed as a biomarker for hepatic cyst infection. Positron-emission tomography after intravenous injection of 18-fluorodeoxyglucose, combined with CT, proved superior to radiological imaging techniques for the identification and localization of kidney and liver pyocyst. This review summarizes the attributes and limitations of these recent clinical, biological and imaging advances in the diagnosis of cyst infection in patients with ADPKD. [less ▲]

Detailed reference viewed: 27 (7 ULg)
Full Text
Peer Reviewed
See detailAMP-activated protein kinase (AMPK) activation and glycogen synthase kinase-3beta (GSK-3beta) inhibition induce Ca2+-independent deposition of tight junction components at the plasma membrane.
Zhang, Lihong ULg; JOURET, François ULg; Rinehart, Jesse et al

in Journal of Biological Chemistry (2011), 286(19), 16879-90

Extracellular Ca(2+) is essential for the development of stable epithelial tight junctions. We find that in the absence of extracellular Ca(2+), AMP-activated protein kinase (AMPK) activation and glycogen ... [more ▼]

Extracellular Ca(2+) is essential for the development of stable epithelial tight junctions. We find that in the absence of extracellular Ca(2+), AMP-activated protein kinase (AMPK) activation and glycogen synthase kinase (GSK)-3beta inhibition independently induce the localization of epithelial tight junction components to the plasma membrane. The Ca(2+)-independent deposition of junctional proteins induced by AMPK activation and GSK-3beta inhibition is independent of E-cadherin. Furthermore, the nectin-afadin system is required for the deposition of tight junction components induced by AMPK activation, but it is not required for that induced by GSK-3beta inhibition. Phosphorylation studies demonstrate that afadin is a substrate for AMPK. These data demonstrate that two kinases involved in regulating cell growth and metabolism act through distinct pathways to influence the deposition of the components of epithelial tight junctions. [less ▲]

Detailed reference viewed: 62 (3 ULg)
Full Text
Peer Reviewed
See detailSegmental and subcellular distribution of CFTR in the kidney.
JOURET, François ULg; Courtoy, Pierre J.; Devuyst, Olivier

in Methods in Molecular Biology (Clifton, N.J.) (2011), 741

Besides its location at the plasma membrane, CFTR is present in intracellular vesicles along both the exocytic and the endocytic pathways. Immunostaining and subcellular fractionation studies of mouse ... [more ▼]

Besides its location at the plasma membrane, CFTR is present in intracellular vesicles along both the exocytic and the endocytic pathways. Immunostaining and subcellular fractionation studies of mouse kidney demonstrate that CFTR is located in endosomes of the cells lining the terminal part of the proximal tubule (PT). The PT cells efficiently reabsorb the ultrafiltered low molecular weight (LMW) proteins by apical endocytosis involving the multiligand receptors megalin and cubilin. The progression from early endosomes to lysosomes depends on the integrity of the cytoskeleton, as well as on vesicular acidification. The latter is mediated by the vacuolar H+-ATPase (V-ATPase) and requires an anionic conductance to dissipate the transmembrane potential gradient. CFTR might ensure such chloride conductance, thereby participating to endosomal acidification and protein uptake by PT cells. Immunostaining with well-characterized antibodies shows that CFTR is located in the terminal segment of PT, where it co-distributes with megalin and cubilin. Subcellular fractionation of total mouse kidneys through Percoll gradients demonstrates the co-localization of CFTR with the V-ATPase and early endosome markers including the Cl-/H+ exchanger, ClC-5, and the small GTPase, Rab5a. Deglycosylation studies and immunoblotting show a distinct glycosylation pattern for CFTR in mouse kidney and lung. The segmental and subcellular distribution of CFTR in mouse kidney supports a role for CFTR in PT receptor-mediated endocytosis of ultrafiltered LMW proteins. [less ▲]

Detailed reference viewed: 14 (0 ULg)
Full Text
Peer Reviewed
See detailPositron-emission computed tomography in cyst infection diagnosis in patients with autosomal dominant polycystic kidney disease.
JOURET, François ULg; Lhommel, Renaud; Beguin, Claire et al

in Clinical Journal of the American Society of Nephrology (2011), 6(7), 1644-50

BACKGROUND: Cyst infection remains a challenging issue in patients with autosomal dominant polycystic kidney disease (ADPKD). In most patients, conventional imaging techniques are inconclusive. Isolated ... [more ▼]

BACKGROUND: Cyst infection remains a challenging issue in patients with autosomal dominant polycystic kidney disease (ADPKD). In most patients, conventional imaging techniques are inconclusive. Isolated observations suggest that (18)fluorodeoxyglucose ((1)(8)FDG) positron-emission computed tomography (PET/CT) might help detect cyst infection in ADPKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Comparative assessment of administrative databases from January 2005 to December 2009 identified 27 PET/CT scans performed in 24 ADPKD patients for suspicion of abdominal infection. Cyst infection was definite if confirmed by cyst fluid analysis. Cyst infection was probable if all four of the following criteria were met: temperature of >38 degrees C for >3 days, loin or liver tenderness, C-reactive protein plasma level of >5 mg/dl, and no CT evidence for intracystic bleeding. Episodes with only two or three criteria were grouped as "fever of unknown origin". RESULTS: Thirteen infectious events in 11 patients met all criteria for kidney (n = 3) or liver (n = 10) cyst infection. CT was contributive in only one patient, whereas PET/CT proved cyst infection in 11 patients (84.6%). In addition, 14 episodes of "fever of unknown origin" in 13 patients were recorded. PET/CT identified the source of infection in nine patients (64.3%), including 2 renal cyst infections. Conversely, PET/CT showed no abnormal (1)(8)FDG uptake in 5 patients, including 2 intracystic bleeding. The median delay between the onset of symptoms and PET/CT procedure was 9 days. CONCLUSIONS: This retrospective series underscores the usefulness of PET/CT to confirm and locate cyst infection and identify alternative sources of abdominal infection in ADPKD patients. [less ▲]

Detailed reference viewed: 23 (5 ULg)
Full Text
Peer Reviewed
See detailDecreased renal accumulation of aminoglycoside reflects defective receptor-mediated endocytosis in cystic fibrosis and Dent's disease.
Raggi, Claudia; Fujiwara, Kunio; Leal, Teresinha et al

in Pflügers Archiv : European Journal of Physiology (2011), 462(6), 851-60

The clinical use of aminoglycoside (AG) antibiotics is limited by their renal toxicity, which is caused by drug accumulation in proximal tubule (PT) cells. Clinical studies reported that renal clearance ... [more ▼]

The clinical use of aminoglycoside (AG) antibiotics is limited by their renal toxicity, which is caused by drug accumulation in proximal tubule (PT) cells. Clinical studies reported that renal clearance of AG is enhanced in cystic fibrosis (CF) patients, which might reflect the role of CFTR in PT cell endocytosis. In order to assess the role of chloride transporters on the renal handling of AG, we investigated gentamicin uptake and renal accumulation in mice lacking functional CFTR (Cftr ( F/F)) or knock-out for the Cl(-)/H(+) exchanger ClC-5 (Clcn5 ( Y/- )). The latter represent a paradigm of PT dysfunction and defective receptor-mediated endocytosis. As compared with controls, Cftr ( F/F) and Clcn5 ( Y/- ) mice showed a 15% to 85% decrease in gentamicin accumulation in the kidney, respectively, in absence of renal failure. Studies on primary cultures of Cftr ( F/F) and Clcn5 ( Y/- ) mouse PT cells confirmed the reduction in gentamicin uptake, although colocalization with endosomes and lysosomes was maintained. Quantification of endocytosis in PT cells revealed that gentamicin, similar to albumin, preferentially binds to megalin. The functional loss of ClC-5 or CFTR was reflected by a decrease of the endocytic uptake of gentamicin, with a more pronounced effect in cells lacking ClC-5. These results support the concept that CFTR, as well as ClC-5, plays a relevant role in PT cell endocytosis. They also demonstrate that the functional loss of these two chloride transporters is associated with impaired uptake of AG in PT cells, reflected by a decreased renal accumulation of the drug. [less ▲]

Detailed reference viewed: 12 (0 ULg)
Full Text
Peer Reviewed
See detailPneumatosis intestinalis and arcuate ligament.
JOURET, François ULg; Dupont, M.; Jouret-Mourin, A. et al

in Acta Clinica Belgica (2010), 65(2), 138-9

Detailed reference viewed: 4 (1 ULg)
Full Text
Peer Reviewed
See detailDelayed colopericardial fistula and pyopneumopericardium.
JOURET, François ULg; Castanares-Zapatero, Diego; Laterre, Pierre-Francois

in Intensive Care Medicine (2010), 36(3), 557-8

Detailed reference viewed: 15 (0 ULg)
Full Text
Peer Reviewed
See detailCLC-5 and KIF3B interact to facilitate CLC-5 plasma membrane expression, endocytosis, and microtubular transport: relevance to pathophysiology of Dent's disease.
Reed, Anita A. C.; Loh, Nellie Y.; Terryn, Sara et al

in American Journal of Physiology - Renal Physiology (2010), 298(2), 365-80

Renal tubular reabsorption is important for extracellular fluid homeostasis and much of this occurs via the receptor-mediated endocytic pathway. This pathway is disrupted in Dent's disease, an X-linked ... [more ▼]

Renal tubular reabsorption is important for extracellular fluid homeostasis and much of this occurs via the receptor-mediated endocytic pathway. This pathway is disrupted in Dent's disease, an X-linked renal tubular disorder that is characterized by low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, and renal failure. Dent's disease is due to mutations of CLC-5, a chloride/proton antiporter, expressed in endosomes and apical membranes of renal tubules. Loss of CLC-5 function alters receptor-mediated endocytosis and trafficking of megalin and cubilin, although the underlying mechanisms remain to be elucidated. Here, we report that CLC-5 interacts with kinesin family member 3B (KIF3B), a heterotrimeric motor protein that facilitates fast anterograde translocation of membranous organelles. Using yeast two-hybrid, glutathione-S-transferase pull-down and coimmunoprecipitation assays, the COOH terminus of CLC-5 and the coiled-coil and globular domains of KIF3B were shown to interact. This was confirmed in vivo by endogenous coimmunoprecipitation of CLC-5 and KIF3B and codistribution with endosomal markers in mouse kidney fractions. Confocal live cell imaging in kidney cells further demonstrated association of CLC-5 and KIF3B, and transport of CLC-5-containing vesicles along KIF3B microtubules. KIF3B overexpression and underexpression, using siRNA, had reciprocal effects on whole cell chloride current amplitudes, CLC-5 cell surface expression, and endocytosis of albumin and transferrin. Clcn5(Y/-) mouse kidneys and isolated proximal tubular polarized cells showed increased KIF3B expression, whose effects on albumin endocytosis were dependent on CLC-5 expression. Thus, the CLC-5 and KIF3B interaction is important for CLC-5 plasma membrane expression and for facilitating endocytosis and microtubular transport in the kidney. [less ▲]

Detailed reference viewed: 15 (0 ULg)
Full Text
Peer Reviewed
See detailGlomerular and proximal tubule cysts as early manifestations of Pkd1 deletion.
Ahrabi, Ali K.; JOURET, François ULg; Marbaix, Etienne et al

in Nephrology Dialysis Transplantation (2010), 25(4), 1067-78

BACKGROUND: The homozygous deletion of Pkd1 in the mouse results in embryonic lethality with renal cysts and hydrops fetalis, but there is no precise data on the segmental origin of cysts and potential ... [more ▼]

BACKGROUND: The homozygous deletion of Pkd1 in the mouse results in embryonic lethality with renal cysts and hydrops fetalis, but there is no precise data on the segmental origin of cysts and potential changes associated with polyhydramnios. METHODS: We used Pkd1-null mice to investigate cystogenesis and analyze the amniotic fluid composition from embryonic day 12.5 (E12.5) to birth (n = 257 embryos). RESULTS: Polyhydramnios was consistently observed from E13.5 in Pkd1(-/-) embryos, in absence of placental abnormalities but with a significantly higher excretion of sodium and glucose from E13.5 through E16.5, and increased cyclic adenosine 3'5-monophosphate (cAMP) levels at E14.5 and E15.5. The Pkd1(-/-) embryos started to die at E13.5, with lethality peaking at E15.5, corresponding to the onset of cystogenesis. The first cysts in Pkd1(-/-) kidneys emerged at E15.5 in mesenchyme-derived segments at the cortico-medullary junction, with a majority of glomerular cysts and fewer proximal tubule cysts (positive for megalin). The cysts extended to ureteric bud-derived collecting ducts (positive for Dolichos biflorus agglutinin lectin) from E16.5. CONCLUSIONS: These studies indicate that Pkd1 deletion is associated with a massive loss of solutes (from E13.5) and increased cAMP levels (E14.5) associated with polyhydramnios. These abnormalities precede renal cysts (E15.5), first derived from glomeruli and proximal tubules and later from the collecting ducts, reflecting the expression pattern of Pkd1 in maturing epithelial cells. [less ▲]

Detailed reference viewed: 16 (0 ULg)