Nous rapportons ici un cas de péritonite à Raoultella planticola multisensible chez un patient im... more Nous rapportons ici un cas de péritonite à Raoultella planticola multisensible chez un patient immunodéprimé en dialyse péritonéale automatisée. Le patient avait travaillé à l’ensablement d’une piste équestre 48 heures auparavant. L’évolution clinique et biologique a été rapidement favorable sous antibiothérapie par ciprofloxacine. La ciprofloxacine est remplacée dans un second temps par de l’amoxyclavulanate en raison d’une tendinopathie achiléenne. L’antibiothérapie est poursuivie pour une durée totale de 3 semaines avec une bonne réponse clinique.Aucun autre cas de péritonite à raoultella n’a été rapporté à ce jour auprès du registre de Dialyse Péritonéale de Langue Française.
Journal of the American Society of Nephrology, 2000
Long-term peritoneal dialysis (PD) is associated with alterations in peritoneal permeability and ... more Long-term peritoneal dialysis (PD) is associated with alterations in peritoneal permeability and loss of ultrafiltration. These changes originate from increased peritoneal surface area, but the morphologic and molecular mechanisms involved remain unknown. The hypothesis that modifications of activity and/or expression of nitric oxide synthase (NOS) isozymes might play a role in these modifications, via enhanced local production of nitric oxide, was tested in this study. NOS activities were measured by the L-citrulline assay in peritoneal biopsies from seven control subjects, eight uremic patients immediately before the onset of PD, and 13 uremic patients on short-term (Ͻ18 mo, n ϭ 6) or long-term (Ͼ18 mo, n ϭ 7) PD. Peritoneal NOS activity is increased fivefold in long-term PD patients compared with control subjects. In uremic patients, NOS activity is positively correlated with the duration of PD. Increased NOS activity is mediated solely by Ca 2ϩ-dependent
Journal of the American Society of Nephrology, 1999
The loss of ultrafiltration (UF) that accompanies acute peritonitis is a common problem in perito... more The loss of ultrafiltration (UF) that accompanies acute peritonitis is a common problem in peritoneal dialysis (PD). It has been suggested that changes in nitric oxide (NO)mediated vascular tone and permeability might be involved in the loss of UF, whereas channel-mediated water permeability should not be affected. This study used a model of acute peritonitis in rats to characterize changes in PD parameters, in correlation with: (1) expression studies of water channel aquaporin-1 and NO synthase (NOS) isoforms and (2) enzymatic assays for NOS in the peritoneum. Compared with controls, rats with peritonitis had a higher removal of plasma urea, a faster glucose absorption, and a loss of UF. Additional changes, including high protein loss, elevated leukocyte counts in dialysate, positive bacterial cultures, edema, and mononu-clear infiltrates, were similar to those observed in PD patients with acute peritonitis. Acute peritonitis in rats induced a major increase in total NOS activity, which was inversely correlated with free-water permeability. The increased NOS activity was mediated by both inducible (Ca 2ϩ-independent) and endothelial (Ca 2ϩ-dependent) NOS isoforms and was reflected by increased peritoneal staining for nitrotyrosine. In contrast, aquaporin-1 expression was unchanged in rats with peritonitis. These findings cast light on the pathophysiology of permeability changes and loss of UF that characterize acute peritonitis. In particular, these data suggest that a local production of NO, mediated by different NOS isoforms, might play a key role in these changes.
Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, 1996
CAPD peritonitis needs to be treated without delay, on an empirical basis, without the results of... more CAPD peritonitis needs to be treated without delay, on an empirical basis, without the results of the dialysate culture (1-4). Selected antibiotics should thus be effective against the most likely infecting pathogens, that is, gram-positive and gram-negative organisms. An Advisory Committee (5) recently recommended the intraperitoneal (IP) administration of vancomycin, together with ceftazidime or aminoglycosides. Unfortunately , the addition of antibiotics to the dialysate bags is cumbersome and carries a theoretical risk of adding new germs to the peritoneal cavity. We therefore decided to explore the feasibility and efficiency of a systemic administration ofvancomycin and ciprofloxacin. Such an antibiotic association should be safe, easy to administer, and efficient. We report our preliminary results here.
Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, 2004
Objectives Peritonitis due to peritoneal dialysis (PD) is best treated empirically while waiting ... more Objectives Peritonitis due to peritoneal dialysis (PD) is best treated empirically while waiting for the results of the dialysate culture. Thus, antibiotic therapy must cover both gram-positive and gram-negative micro-organisms. First, over a period of 9 years in a multicenter study we evaluated the efficiency of a vancomycin and ciprofloxacin combination given as the first-line treatment protocol for PD peritonitis. Second, we evaluated whether a systemic route of administration of the antibiotics could be an interesting alternative to the usual cumbersome intraperitoneal drug administration. Methods Vancomycin 15 mg/kg body weight, intravenous, and oral ciprofloxacin 250 mg two times per day (500 mg twice per day if residual creatinine clearance was above 3 mL/minute) were prescribed at diagnosis of peritonitis. Vancomycin injections were repeated (when blood trough level was expected to be below 12 μg/mL) in cases of gram-positive organisms for a total duration of 3 weeks. Ciprof...
American Journal of Physiology-Heart and Circulatory Physiology, 1998
Water transport during peritoneal dialysis (PD) requires ultrasmall pores in the capillary endoth... more Water transport during peritoneal dialysis (PD) requires ultrasmall pores in the capillary endothelium of the peritoneum and is impaired in the case of peritoneal inflammation. The water channel aquaporin (AQP)-1 has been proposed to be the ultrasmall pore in animal models. To substantiate the role of AQP-1 in the human peritoneum, we investigated the expression of AQP-1, AQP-2, and endothelial nitric oxide synthase (eNOS) in 19 peritoneal samples from normal subjects ( n = 5), uremic patients treated by hemodialysis ( n = 7) or PD ( n = 4), and nonuremic patients ( n = 3), using Western blotting and immunostaining. AQP-1 is very specifically located in capillary and venule endothelium but not in small-size arteries. In contrast, eNOS is located in all types of endothelia. Immunoblot for AQP-1 in human peritoneum reveals a 28-kDa band (unglycosylated AQP-1) and diffuse bands of 35–50 kDa (glycosylated AQP-1). Although AQP-1 expression is remarkably stable in all samples whatever the...
Journal of the American Society of Nephrology : JASN, 2018
Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritone... more Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated. We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin. modeling and studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, co...
Journal of the American Society of Nephrology, 2017
Bacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). Du... more Bacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). During peritonitis, the peritoneal membrane undergoes structural and functional alterations that are mediated by IL-1b. The NLRP3 inflammasome is a caspase-1-activating multiprotein complex that links sensing of microbial and stress products to activation of proinflammatory cytokines, including IL-1b. The potential roles of the NLRP3 inflammasome and IL-1b in the peritoneal membrane during acute peritonitis have not been investigated. Here, we show that the NLRP3 inflammasome is activated during acute bacterial peritonitis in patients on PD, and this activation associates with the release of IL-1b in the dialysate. In mice, lipopolysaccharide-or Escherichia coli-induced peritonitis led to IL-1b release in the peritoneal membrane. The genetic deletion of Nalp3, which encodes NLRP3, abrogated defects in solute transport during acute peritonitis and restored ultrafiltration. In human umbilical vein endothelial cells, IL-1b treatment directly enhanced endothelial cell proliferation and increased microvascular permeability. These in vitro effects require endothelial IL-1 receptors, shown by immunofluorescence to be expressed in peritoneal capillaries in mice. Furthermore, administration of the IL-1b receptor antagonist, anakinra, efficiently decreased nitric oxide production and vascular proliferation and restored peritoneal function in mouse models of peritonitis, even in mice treated with standard-of-care antibiotherapy. These data demonstrate that NLRP3 activation and IL-1b release have a critical role in solute transport defects and tissue remodeling during PD-related peritonitis. Blockade of the NLRP3/IL-1b axis offers a novel method for rescuing morphologic alterations and transport defects during acute peritonitis.
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis, Sep 9, 2016
Peritonitis is a common and serious complication of peritoneal dialysis (PD). Although less than ... more Peritonitis is a common and serious complication of peritoneal dialysis (PD). Although less than 5% of peritonitis episodes result in death, peritonitis is the direct or major contributing cause of death in around 16% of PD patients (1-6). In addition, severe or prolonged peritonitis leads to structural and functional alterations of the peritoneal membrane, eventually leading to membrane failure. Peritonitis is a major cause of PD technique failure and conversion to long-term hemodialysis (1,5,7,8). Recommendations under the auspices of the International Society for Peritoneal Dialysis (ISPD) were first published in 1983 and revised in 1993, 1996, 2000, 2005, and 2010 (9-14). The present recommendations are organized into 5 sections: 1. Peritonitis rate 2. Prevention of peritonitis 3. Initial presentation and management of peritonitis 4. Subsequent management of peritonitis 5.
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
Fifteen years ago, our group reported the case of a 67-year-old man on peritoneal dialysis for 11... more Fifteen years ago, our group reported the case of a 67-year-old man on peritoneal dialysis for 11 years, in whom ultrafiltration failure and impaired sodium sieving were associated with an apparently normal expression of aquaporin-1 (AQP1) water channels in peritoneal capillaries. At that time, AQP1 dysfunction was suggested as the cause of impaired free-water transport. However, recent data from computer simulations, and structural and functional analysis of the peritoneal membrane of patients with encapsulating peritoneal sclerosis, demonstrated that changes in the peritoneal interstitium directly alter osmotic water transport. In light of these insights, we challenge the initial hypothesis and provide several lines of evidence supporting the diagnosis of encapsulating peritoneal sclerosis in this patient and suggesting that severe peritoneal fibrosis accounted for the loss of osmotic conductance developed during the course of peritoneal dialysis.
Simvastatin is among the most commonly used prescription medications for cholesterol reduction an... more Simvastatin is among the most commonly used prescription medications for cholesterol reduction and the most common statin-related adverse drug reaction is skeletal muscle toxicity. Multiple factors have been shown to influence simvastatin-induced myopathy. In addition to age, gender, ethnicity, genetic predisposition, and dose, drug-drug interactions play a major role. This is particularly true for drugs that are extensively metabolized by cytochrome P450 (CYP)3A4. We describe a particularly severe case of rhabdomyolysis after the introduction of ciprofloxacin, a weak CYP3A4 inhibitor, in a patient who previously tolerated the simvastatin-amlodipine combination.
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
Periostin is a matricellular protein involved in tissue remodeling through the promotion of adhes... more Periostin is a matricellular protein involved in tissue remodeling through the promotion of adhesion, cell survival, cellular dedifferentiation, and fibrogenesis. It can be induced by transforming growth factor beta and high glucose concentrations. We hypothesized that this protein might be expressed in the peritoneal cavity of patients on peritoneal dialysis (PD) and even more in patients with signs of encapsulating peritoneal sclerosis (EPS). In this retrospective study, we included peritoneal biopsies from patients on PD with EPS (n = 7) and without signs of EPS (n = 10), and we compared them with biopsies taken during hernia repair from patients not on PD (n = 11) and during various procedures from uremic patients not on PD (n = 6). Periostin was localized by immunohistochemistry, scored semiquantitatively, and quantified by morphometry. Periostin protein concentrations were measured by ELISA in dialysates from 15 patients. Periostin messenger RNA was quantified in vitro in peri...
Journal of the American Society of Nephrology, 2015
Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis... more Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.
The effects of normal as compared with low hematocrit values in patients with cardiac disease who... more The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin [see comments].
Background. Water transport in peritoneal dialysis (PD) patients occurs through the small pores a... more Background. Water transport in peritoneal dialysis (PD) patients occurs through the small pores and water channels, the latter allowing free water transport (FWT). The osmotic gradient is known to be one of the major determinants of water transport. The objective of the study was to analyse the relation between each transport route and the osmotic gradient. Methods. The 4-h standard peritoneal permeability analyses of 80 stable PD patients were studied. Small pore transport (SPT) was calculated based on the transported amount of sodium. FWT was calculated by subtracting SPT from transcapillary ultrafiltration (TCUF). Water transport rates were determined. The osmotic gradient was calculated. The slope of the relation between FWT rate and osmotic gradient (slope FWT), and the elimination constant (K e) of the exponential relation between SPT rate and osmotic gradient (K SPT) were calculated for every patient. Results. The FWT rate was related to the osmotic gradient (P = 0.001). A similar correlation was also found between the SPT rate and osmotic gradient when fitted exponentially (P = 0.005). The rates of FWT decreased significantly between each time point during the whole dwell. The SPT rates decreased significantly within the first half of the dwell and levelled off thereafter. No correlations were found between the slope FWT , K SPT and PD duration. The slope FWT of the relationship between the FWT and the osmotic gradient is an indirect measurement of the amount of functioning water channels. Similarly, the K SPT value represents the number of functioning small pores. The absence of a relationship of these parameters with the duration of PD suggests opposing mechanisms, for instance a lower number of functioning pores in combination with an increased vascular surface area. Conclusion. The curves of the relationship between FWR, SPT and OG support the assumption that FWR is much more dependent on the OG than SPT. Non-osmotic
Background. The clinical determinants of baseline peritoneal membrane (PM) transport characterist... more Background. The clinical determinants of baseline peritoneal membrane (PM) transport characteristics, as evaluated by a hypertonic peritoneal equilibration test (PET), remain ill-defined. Likewise, the longitudinal evolution of PM transport properties in peritoneal dialysis (PD) patients given automated PD (APD) and icodextrin still needs to be determined precisely. The aims of the present study were (1) to determine the clinical and biological factors affecting PM transport characteristics at PD onset and (2) to assess the longitudinal evolution of these markers. Methods. Seventy-two consecutive patients performed a baseline 3.86% glucose dialysate PET and were enrolled. Subgroups of 35 and 18 patients underwent another PET 1 and 2 year(s) later, respectively, and were included in the longitudinal part. For each patient, clinical and biological data were reviewed and PM transport markers calculated. Results. At onset of PD, angiotensin-converting enzyme (ACE) inhibitor intake (r ¼ 0.31, P ¼ 0.01), presence of a diabetes (r ¼ 0.26, P ¼ 0.03) and body surface area (BSA) (r ¼ 0.26, P ¼ 0.03) independently affected the mass transfer area coefficient (MTAC) of creatinine. Serum albumin (r ¼ À0.46, P<0.001) and net ultrafiltration (r ¼ À0.33, P ¼ 0.009) inversely correlated with MTAC creatinine. Sodium sieving was inversely correlated with BSA (r ¼ À0.33, P ¼ 0.01). Serum albumin also inversely correlated with albumin clearance (r ¼ À0.39, P ¼ 0.02). Finally, the independent covariates that affected a2-macroglobulin clearance were age (P ¼ 0.03), diabetes (P ¼ 0.01) and the level of residual renal function (P<0.01). Serum albumin decreased with time on PD (P ¼ 0.02). A rise in small solute transport and a decrease in net ultrafiltration, but no change in protein clearances, were also observed after 2 years of PD. Conclusions. Transport properties across the PM, as evaluated by MTAC creatinine and sodium sieving determinations, are correlated with anthropometric characteristics (BSA) and by comorbid conditions (witnessed by the presence of diabetes, a low serum albumin concentration and the prescription of an ACE inhibitor). The short-term evolution (2 years) of the PM transport properties of patients on APD and icodextrin is still characterized by a progressive increase in small solute transport and a loss of ultrafiltration capacity, as documented in ancient studies, but not with a modification in protein clearances. This conclusion merits, however, to be further evaluated in a larger cohort of PD patients after a longer follow-up.
Background. Functional variants in the IL6 gene, in particular the −174G/C polymorphism (rs180079... more Background. Functional variants in the IL6 gene, in particular the −174G/C polymorphism (rs1800795), affect the mortality risk in dialysis patients. Peritoneal dialysis (PD) patients harbouring the C allele of the −174G/C polymorphism of IL6 showed faster peritoneal transport. The aim of this study was to investigate this IL6 variant as risk factor for mortality and technique failure in a large cohort of Caucasian PD patients. Methods. A Dutch multicentre cohort of 398 incident PD patients (NECOSAD) was analysed. Survival analysis was performed for death and technique failure with a maximum follow-up of 5 years. A combined PD cohort from Amsterdam (Academic Medical Center, N = 71) and Brussels (Université catholique de Louvain Medical School, N = 102) was used for independent replication. Results. In NECOSAD, 105 patients died on dialysis [incidence rate 10.3/100 person-years (py)], and 138 patients experienced technique failure (16.2/100 py), with peritonitis as important cause. Patients with the C/C genotype had a 71% increased mortality risk compared to patients with the G/G genotype (95% confidence interval 0.98-2.98); this effect was mainly a long-term effect: a 2.7-fold increased mortality risk was found in patients having survived 2 years since the start on dialysis, and a 1.7-fold increased risk for the combined end point (mortality or technique failure). In the combined replication cohort, no increased risks were found in patients with the C/C genotype. Conclusions. The C/C genotype of the −174G/C polymorphism was associated with an increased mortality risk in 398 Dutch incident PD patients. The existence of substantial differences between the two academic replication cohorts and the discovery cohort from NECOSAD and the limited power of these cohorts prevented an independent replication of the NECOSAD findings.
Nous rapportons ici un cas de péritonite à Raoultella planticola multisensible chez un patient im... more Nous rapportons ici un cas de péritonite à Raoultella planticola multisensible chez un patient immunodéprimé en dialyse péritonéale automatisée. Le patient avait travaillé à l’ensablement d’une piste équestre 48 heures auparavant. L’évolution clinique et biologique a été rapidement favorable sous antibiothérapie par ciprofloxacine. La ciprofloxacine est remplacée dans un second temps par de l’amoxyclavulanate en raison d’une tendinopathie achiléenne. L’antibiothérapie est poursuivie pour une durée totale de 3 semaines avec une bonne réponse clinique.Aucun autre cas de péritonite à raoultella n’a été rapporté à ce jour auprès du registre de Dialyse Péritonéale de Langue Française.
Journal of the American Society of Nephrology, 2000
Long-term peritoneal dialysis (PD) is associated with alterations in peritoneal permeability and ... more Long-term peritoneal dialysis (PD) is associated with alterations in peritoneal permeability and loss of ultrafiltration. These changes originate from increased peritoneal surface area, but the morphologic and molecular mechanisms involved remain unknown. The hypothesis that modifications of activity and/or expression of nitric oxide synthase (NOS) isozymes might play a role in these modifications, via enhanced local production of nitric oxide, was tested in this study. NOS activities were measured by the L-citrulline assay in peritoneal biopsies from seven control subjects, eight uremic patients immediately before the onset of PD, and 13 uremic patients on short-term (Ͻ18 mo, n ϭ 6) or long-term (Ͼ18 mo, n ϭ 7) PD. Peritoneal NOS activity is increased fivefold in long-term PD patients compared with control subjects. In uremic patients, NOS activity is positively correlated with the duration of PD. Increased NOS activity is mediated solely by Ca 2ϩ-dependent
Journal of the American Society of Nephrology, 1999
The loss of ultrafiltration (UF) that accompanies acute peritonitis is a common problem in perito... more The loss of ultrafiltration (UF) that accompanies acute peritonitis is a common problem in peritoneal dialysis (PD). It has been suggested that changes in nitric oxide (NO)mediated vascular tone and permeability might be involved in the loss of UF, whereas channel-mediated water permeability should not be affected. This study used a model of acute peritonitis in rats to characterize changes in PD parameters, in correlation with: (1) expression studies of water channel aquaporin-1 and NO synthase (NOS) isoforms and (2) enzymatic assays for NOS in the peritoneum. Compared with controls, rats with peritonitis had a higher removal of plasma urea, a faster glucose absorption, and a loss of UF. Additional changes, including high protein loss, elevated leukocyte counts in dialysate, positive bacterial cultures, edema, and mononu-clear infiltrates, were similar to those observed in PD patients with acute peritonitis. Acute peritonitis in rats induced a major increase in total NOS activity, which was inversely correlated with free-water permeability. The increased NOS activity was mediated by both inducible (Ca 2ϩ-independent) and endothelial (Ca 2ϩ-dependent) NOS isoforms and was reflected by increased peritoneal staining for nitrotyrosine. In contrast, aquaporin-1 expression was unchanged in rats with peritonitis. These findings cast light on the pathophysiology of permeability changes and loss of UF that characterize acute peritonitis. In particular, these data suggest that a local production of NO, mediated by different NOS isoforms, might play a key role in these changes.
Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, 1996
CAPD peritonitis needs to be treated without delay, on an empirical basis, without the results of... more CAPD peritonitis needs to be treated without delay, on an empirical basis, without the results of the dialysate culture (1-4). Selected antibiotics should thus be effective against the most likely infecting pathogens, that is, gram-positive and gram-negative organisms. An Advisory Committee (5) recently recommended the intraperitoneal (IP) administration of vancomycin, together with ceftazidime or aminoglycosides. Unfortunately , the addition of antibiotics to the dialysate bags is cumbersome and carries a theoretical risk of adding new germs to the peritoneal cavity. We therefore decided to explore the feasibility and efficiency of a systemic administration ofvancomycin and ciprofloxacin. Such an antibiotic association should be safe, easy to administer, and efficient. We report our preliminary results here.
Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, 2004
Objectives Peritonitis due to peritoneal dialysis (PD) is best treated empirically while waiting ... more Objectives Peritonitis due to peritoneal dialysis (PD) is best treated empirically while waiting for the results of the dialysate culture. Thus, antibiotic therapy must cover both gram-positive and gram-negative micro-organisms. First, over a period of 9 years in a multicenter study we evaluated the efficiency of a vancomycin and ciprofloxacin combination given as the first-line treatment protocol for PD peritonitis. Second, we evaluated whether a systemic route of administration of the antibiotics could be an interesting alternative to the usual cumbersome intraperitoneal drug administration. Methods Vancomycin 15 mg/kg body weight, intravenous, and oral ciprofloxacin 250 mg two times per day (500 mg twice per day if residual creatinine clearance was above 3 mL/minute) were prescribed at diagnosis of peritonitis. Vancomycin injections were repeated (when blood trough level was expected to be below 12 μg/mL) in cases of gram-positive organisms for a total duration of 3 weeks. Ciprof...
American Journal of Physiology-Heart and Circulatory Physiology, 1998
Water transport during peritoneal dialysis (PD) requires ultrasmall pores in the capillary endoth... more Water transport during peritoneal dialysis (PD) requires ultrasmall pores in the capillary endothelium of the peritoneum and is impaired in the case of peritoneal inflammation. The water channel aquaporin (AQP)-1 has been proposed to be the ultrasmall pore in animal models. To substantiate the role of AQP-1 in the human peritoneum, we investigated the expression of AQP-1, AQP-2, and endothelial nitric oxide synthase (eNOS) in 19 peritoneal samples from normal subjects ( n = 5), uremic patients treated by hemodialysis ( n = 7) or PD ( n = 4), and nonuremic patients ( n = 3), using Western blotting and immunostaining. AQP-1 is very specifically located in capillary and venule endothelium but not in small-size arteries. In contrast, eNOS is located in all types of endothelia. Immunoblot for AQP-1 in human peritoneum reveals a 28-kDa band (unglycosylated AQP-1) and diffuse bands of 35–50 kDa (glycosylated AQP-1). Although AQP-1 expression is remarkably stable in all samples whatever the...
Journal of the American Society of Nephrology : JASN, 2018
Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritone... more Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated. We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin. modeling and studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, co...
Journal of the American Society of Nephrology, 2017
Bacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). Du... more Bacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). During peritonitis, the peritoneal membrane undergoes structural and functional alterations that are mediated by IL-1b. The NLRP3 inflammasome is a caspase-1-activating multiprotein complex that links sensing of microbial and stress products to activation of proinflammatory cytokines, including IL-1b. The potential roles of the NLRP3 inflammasome and IL-1b in the peritoneal membrane during acute peritonitis have not been investigated. Here, we show that the NLRP3 inflammasome is activated during acute bacterial peritonitis in patients on PD, and this activation associates with the release of IL-1b in the dialysate. In mice, lipopolysaccharide-or Escherichia coli-induced peritonitis led to IL-1b release in the peritoneal membrane. The genetic deletion of Nalp3, which encodes NLRP3, abrogated defects in solute transport during acute peritonitis and restored ultrafiltration. In human umbilical vein endothelial cells, IL-1b treatment directly enhanced endothelial cell proliferation and increased microvascular permeability. These in vitro effects require endothelial IL-1 receptors, shown by immunofluorescence to be expressed in peritoneal capillaries in mice. Furthermore, administration of the IL-1b receptor antagonist, anakinra, efficiently decreased nitric oxide production and vascular proliferation and restored peritoneal function in mouse models of peritonitis, even in mice treated with standard-of-care antibiotherapy. These data demonstrate that NLRP3 activation and IL-1b release have a critical role in solute transport defects and tissue remodeling during PD-related peritonitis. Blockade of the NLRP3/IL-1b axis offers a novel method for rescuing morphologic alterations and transport defects during acute peritonitis.
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis, Sep 9, 2016
Peritonitis is a common and serious complication of peritoneal dialysis (PD). Although less than ... more Peritonitis is a common and serious complication of peritoneal dialysis (PD). Although less than 5% of peritonitis episodes result in death, peritonitis is the direct or major contributing cause of death in around 16% of PD patients (1-6). In addition, severe or prolonged peritonitis leads to structural and functional alterations of the peritoneal membrane, eventually leading to membrane failure. Peritonitis is a major cause of PD technique failure and conversion to long-term hemodialysis (1,5,7,8). Recommendations under the auspices of the International Society for Peritoneal Dialysis (ISPD) were first published in 1983 and revised in 1993, 1996, 2000, 2005, and 2010 (9-14). The present recommendations are organized into 5 sections: 1. Peritonitis rate 2. Prevention of peritonitis 3. Initial presentation and management of peritonitis 4. Subsequent management of peritonitis 5.
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
Fifteen years ago, our group reported the case of a 67-year-old man on peritoneal dialysis for 11... more Fifteen years ago, our group reported the case of a 67-year-old man on peritoneal dialysis for 11 years, in whom ultrafiltration failure and impaired sodium sieving were associated with an apparently normal expression of aquaporin-1 (AQP1) water channels in peritoneal capillaries. At that time, AQP1 dysfunction was suggested as the cause of impaired free-water transport. However, recent data from computer simulations, and structural and functional analysis of the peritoneal membrane of patients with encapsulating peritoneal sclerosis, demonstrated that changes in the peritoneal interstitium directly alter osmotic water transport. In light of these insights, we challenge the initial hypothesis and provide several lines of evidence supporting the diagnosis of encapsulating peritoneal sclerosis in this patient and suggesting that severe peritoneal fibrosis accounted for the loss of osmotic conductance developed during the course of peritoneal dialysis.
Simvastatin is among the most commonly used prescription medications for cholesterol reduction an... more Simvastatin is among the most commonly used prescription medications for cholesterol reduction and the most common statin-related adverse drug reaction is skeletal muscle toxicity. Multiple factors have been shown to influence simvastatin-induced myopathy. In addition to age, gender, ethnicity, genetic predisposition, and dose, drug-drug interactions play a major role. This is particularly true for drugs that are extensively metabolized by cytochrome P450 (CYP)3A4. We describe a particularly severe case of rhabdomyolysis after the introduction of ciprofloxacin, a weak CYP3A4 inhibitor, in a patient who previously tolerated the simvastatin-amlodipine combination.
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
Periostin is a matricellular protein involved in tissue remodeling through the promotion of adhes... more Periostin is a matricellular protein involved in tissue remodeling through the promotion of adhesion, cell survival, cellular dedifferentiation, and fibrogenesis. It can be induced by transforming growth factor beta and high glucose concentrations. We hypothesized that this protein might be expressed in the peritoneal cavity of patients on peritoneal dialysis (PD) and even more in patients with signs of encapsulating peritoneal sclerosis (EPS). In this retrospective study, we included peritoneal biopsies from patients on PD with EPS (n = 7) and without signs of EPS (n = 10), and we compared them with biopsies taken during hernia repair from patients not on PD (n = 11) and during various procedures from uremic patients not on PD (n = 6). Periostin was localized by immunohistochemistry, scored semiquantitatively, and quantified by morphometry. Periostin protein concentrations were measured by ELISA in dialysates from 15 patients. Periostin messenger RNA was quantified in vitro in peri...
Journal of the American Society of Nephrology, 2015
Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis... more Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.
The effects of normal as compared with low hematocrit values in patients with cardiac disease who... more The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin [see comments].
Background. Water transport in peritoneal dialysis (PD) patients occurs through the small pores a... more Background. Water transport in peritoneal dialysis (PD) patients occurs through the small pores and water channels, the latter allowing free water transport (FWT). The osmotic gradient is known to be one of the major determinants of water transport. The objective of the study was to analyse the relation between each transport route and the osmotic gradient. Methods. The 4-h standard peritoneal permeability analyses of 80 stable PD patients were studied. Small pore transport (SPT) was calculated based on the transported amount of sodium. FWT was calculated by subtracting SPT from transcapillary ultrafiltration (TCUF). Water transport rates were determined. The osmotic gradient was calculated. The slope of the relation between FWT rate and osmotic gradient (slope FWT), and the elimination constant (K e) of the exponential relation between SPT rate and osmotic gradient (K SPT) were calculated for every patient. Results. The FWT rate was related to the osmotic gradient (P = 0.001). A similar correlation was also found between the SPT rate and osmotic gradient when fitted exponentially (P = 0.005). The rates of FWT decreased significantly between each time point during the whole dwell. The SPT rates decreased significantly within the first half of the dwell and levelled off thereafter. No correlations were found between the slope FWT , K SPT and PD duration. The slope FWT of the relationship between the FWT and the osmotic gradient is an indirect measurement of the amount of functioning water channels. Similarly, the K SPT value represents the number of functioning small pores. The absence of a relationship of these parameters with the duration of PD suggests opposing mechanisms, for instance a lower number of functioning pores in combination with an increased vascular surface area. Conclusion. The curves of the relationship between FWR, SPT and OG support the assumption that FWR is much more dependent on the OG than SPT. Non-osmotic
Background. The clinical determinants of baseline peritoneal membrane (PM) transport characterist... more Background. The clinical determinants of baseline peritoneal membrane (PM) transport characteristics, as evaluated by a hypertonic peritoneal equilibration test (PET), remain ill-defined. Likewise, the longitudinal evolution of PM transport properties in peritoneal dialysis (PD) patients given automated PD (APD) and icodextrin still needs to be determined precisely. The aims of the present study were (1) to determine the clinical and biological factors affecting PM transport characteristics at PD onset and (2) to assess the longitudinal evolution of these markers. Methods. Seventy-two consecutive patients performed a baseline 3.86% glucose dialysate PET and were enrolled. Subgroups of 35 and 18 patients underwent another PET 1 and 2 year(s) later, respectively, and were included in the longitudinal part. For each patient, clinical and biological data were reviewed and PM transport markers calculated. Results. At onset of PD, angiotensin-converting enzyme (ACE) inhibitor intake (r ¼ 0.31, P ¼ 0.01), presence of a diabetes (r ¼ 0.26, P ¼ 0.03) and body surface area (BSA) (r ¼ 0.26, P ¼ 0.03) independently affected the mass transfer area coefficient (MTAC) of creatinine. Serum albumin (r ¼ À0.46, P<0.001) and net ultrafiltration (r ¼ À0.33, P ¼ 0.009) inversely correlated with MTAC creatinine. Sodium sieving was inversely correlated with BSA (r ¼ À0.33, P ¼ 0.01). Serum albumin also inversely correlated with albumin clearance (r ¼ À0.39, P ¼ 0.02). Finally, the independent covariates that affected a2-macroglobulin clearance were age (P ¼ 0.03), diabetes (P ¼ 0.01) and the level of residual renal function (P<0.01). Serum albumin decreased with time on PD (P ¼ 0.02). A rise in small solute transport and a decrease in net ultrafiltration, but no change in protein clearances, were also observed after 2 years of PD. Conclusions. Transport properties across the PM, as evaluated by MTAC creatinine and sodium sieving determinations, are correlated with anthropometric characteristics (BSA) and by comorbid conditions (witnessed by the presence of diabetes, a low serum albumin concentration and the prescription of an ACE inhibitor). The short-term evolution (2 years) of the PM transport properties of patients on APD and icodextrin is still characterized by a progressive increase in small solute transport and a loss of ultrafiltration capacity, as documented in ancient studies, but not with a modification in protein clearances. This conclusion merits, however, to be further evaluated in a larger cohort of PD patients after a longer follow-up.
Background. Functional variants in the IL6 gene, in particular the −174G/C polymorphism (rs180079... more Background. Functional variants in the IL6 gene, in particular the −174G/C polymorphism (rs1800795), affect the mortality risk in dialysis patients. Peritoneal dialysis (PD) patients harbouring the C allele of the −174G/C polymorphism of IL6 showed faster peritoneal transport. The aim of this study was to investigate this IL6 variant as risk factor for mortality and technique failure in a large cohort of Caucasian PD patients. Methods. A Dutch multicentre cohort of 398 incident PD patients (NECOSAD) was analysed. Survival analysis was performed for death and technique failure with a maximum follow-up of 5 years. A combined PD cohort from Amsterdam (Academic Medical Center, N = 71) and Brussels (Université catholique de Louvain Medical School, N = 102) was used for independent replication. Results. In NECOSAD, 105 patients died on dialysis [incidence rate 10.3/100 person-years (py)], and 138 patients experienced technique failure (16.2/100 py), with peritonitis as important cause. Patients with the C/C genotype had a 71% increased mortality risk compared to patients with the G/G genotype (95% confidence interval 0.98-2.98); this effect was mainly a long-term effect: a 2.7-fold increased mortality risk was found in patients having survived 2 years since the start on dialysis, and a 1.7-fold increased risk for the combined end point (mortality or technique failure). In the combined replication cohort, no increased risks were found in patients with the C/C genotype. Conclusions. The C/C genotype of the −174G/C polymorphism was associated with an increased mortality risk in 398 Dutch incident PD patients. The existence of substantial differences between the two academic replication cohorts and the discovery cohort from NECOSAD and the limited power of these cohorts prevented an independent replication of the NECOSAD findings.
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Papers by Eric Goffin