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1.
Cell Rep ; 39(10): 110915, 2022 06 07.
Article in English | MEDLINE | ID: mdl-35675784

ABSTRACT

Elucidating the cellular and molecular mechanisms that regulate the balance between progenitor cell proliferation and neuronal differentiation in the construction of the embryonic brain demands the combination of cell lineage and functional approaches. Here, we generate the comprehensive lineage of hindbrain boundary cells by using a CRISPR-based knockin zebrafish transgenic line that specifically labels the boundaries. We unveil that boundary cells asynchronously engage in neurogenesis undergoing a functional transition from neuroepithelial progenitors to radial glia cells, coinciding with the onset of Notch3 signaling that triggers their asymmetrical cell division. Upon notch3 loss of function, boundary cells lose radial glia properties and symmetrically divide undergoing neuronal differentiation. Finally, we show that the fate of boundary cells is to become neurons, the subtype of which relies on their axial position, suggesting that boundary cells contribute to refine the number and proportion of the distinct neuronal populations.


Subject(s)
Asymmetric Cell Division , Zebrafish , Animals , Cell Differentiation , Neurogenesis , Rhombencephalon/metabolism , Zebrafish/metabolism , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism
2.
G3 (Bethesda) ; 11(12)2021 12 08.
Article in English | MEDLINE | ID: mdl-34599810

ABSTRACT

The Drosophila genome contains approximately 14,000 protein-coding genes encoding all the necessary information to sustain cellular physiology, tissue organization, organism development, and behavior. In this manuscript, we describe in some detail the phenotypes in the adult fly wing generated after knockdown of approximately 80% of Drosophila genes. We combined this phenotypic description with a comprehensive molecular classification of the Drosophila proteins into classes that summarize the main expected or known biochemical/functional aspect of each protein. This information, combined with mRNA expression levels and in situ expression patterns, provides a simplified atlas of the Drosophila genome, from housekeeping proteins to the components of the signaling pathways directing wing development, that might help to further understand the contribution of each gene group to wing formation.


Subject(s)
Drosophila Proteins , Drosophila , Animals , Drosophila/genetics , Drosophila/metabolism , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Phenotype , RNA Interference , Wings, Animal/metabolism
3.
G3 (Bethesda) ; 11(12)2021 12 08.
Article in English | MEDLINE | ID: mdl-34599819

ABSTRACT

We have screened a collection of UAS-RNAi lines targeting 10,920 Drosophila protein-coding genes for phenotypes in the adult wing. We identified 3653 genes (33%) whose knockdown causes either larval/pupal lethality or a mutant phenotype affecting the formation of a normal wing. The most frequent phenotypes consist of changes in wing size, vein differentiation, and patterning, defects in the wing margin and in the apposition of the dorsal and ventral wing surfaces. We also defined 16 functional categories encompassing the most relevant aspect of each protein function and assigned each Drosophila gene to one of these functional groups. This allowed us to identify which mutant phenotypes are enriched within each functional group. Finally, we used previously published gene expression datasets to determine which genes are or are not expressed in the wing disc. Integrating expression, phenotypic and molecular information offers considerable precision to identify the relevant genes affecting wing formation and the biological processes regulated by them.


Subject(s)
Drosophila Proteins , Drosophila , Animals , Drosophila/genetics , Drosophila/metabolism , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Gene Expression Regulation, Developmental , Phenotype , RNA Interference , Wings, Animal/metabolism
4.
Sci Adv ; 7(44): eabi7785, 2021 Oct 29.
Article in English | MEDLINE | ID: mdl-34714681

ABSTRACT

Mechanical forces are exerted throughout cytokinesis, the final step of cell division. Yet, how forces are transduced and affect the signaling dynamics of cytokinetic proteins remains poorly characterized. We now show that the mechanosensitive Piezo1 channel is activated at the intercellular bridge (ICB) connecting daughter cells to regulate abscission. Inhibition of Piezo1 caused multinucleation both in vitro and in vivo. Piezo1 positioning at the ICB during cytokinesis depends on Pacsin3. Pharmacological and genetic inhibition of Piezo1 or Pacsin3 resulted in mislocation of Rab11-family-interacting protein 3 (Rab11-FIP3) endosomes, apoptosis-linked gene 2-interacting protein X (ALIX), and endosomal sorting complex required for transport III (ESCRT-III). Furthermore, we identified FIP3 as the link between Piezo1-generated Ca2+ signals and ALIX delivery to the ICB, where ALIX recruits the ESCRT-III component charged multivesicular body protein 4B, which promotes abscission. These results provide a different view of how mechanical forces participate in cytokinesis and identify Piezo1 as a key modulator of endosome trafficking.

5.
J Nephrol ; 34(3): 763-771, 2021 06.
Article in English | MEDLINE | ID: mdl-33387342

ABSTRACT

BACKGROUND AND OBJECTIVES: Autologous arteriovenous fistula (AVF) is the best vascular access for hemodialysis. Distal forearm radiocephalic fistula is the best option, although the primary failure rate ranges from 20% to 50%. The main objective of the PHYSICALFAV trial was to evaluate the effect of preoperative isometric exercise on vascular caliber, percentage of distal arteriovenous fistula, and primary failure rate. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The PHYSICALFAV trial (NCT03213756) is an open-label, multicenter, prospective, randomized, controlled trial (RCT). A total of 138 patients were randomized 1:1 to the exercise group (exercises combining a handgrip device and an elastic band for 8 weeks) or the control group (no exercise) and followed up with periodic Doppler ultrasound (DU) examinations. RESULTS: After 8 weeks of preoperative isometric exercise, in the exercise group, significant increases were detected in venous caliber (2.80 ± 0.95 mm vs 3.52 ± 0.93 mm [p < 0.001]), arterial caliber (2.61 ± 0.82 mm vs 2.74 ± 0.80 mm [p = 0.008]), arterial peak systolic velocity (66.34 ± 19.2 cm/s vs 71.03 ± 21.5 cm/s [p 0.043]), and maximum strength (28.35 ± 9.16 kg vs 32.68 ± 10.8 kg [p < 0.001]). Distal radiocephalic fistulas were performed in 75% of the exercise group patients compared with 50.8% in the control group (p = 0.030). The global primary failure rate was very low in both groups (7% exercise group vs 14% control group [p = 0.373]). CONCLUSION: Isometric preoperative exercise can improve vascular caliber and increase the possibility of performing distal arteriovenous fistula, with no significant differences in primary failure rate.


Subject(s)
Arteriovenous Fistula , Arteriovenous Shunt, Surgical , Arteriovenous Shunt, Surgical/adverse effects , Humans , Preoperative Exercise , Renal Dialysis/adverse effects , Treatment Outcome , Ultrasonography , Vascular Patency
6.
Development ; 146(14)2019 07 22.
Article in English | MEDLINE | ID: mdl-31273051

ABSTRACT

Cells perceive their microenvironment through chemical and physical cues. However, how the mechanical signals are interpreted during embryonic tissue deformation to result in specific cell behaviors is largely unknown. The Yap/Taz family of transcriptional co-activators has emerged as an important regulator of tissue growth and regeneration, responding to physical cues from the extracellular matrix, and to cell shape and actomyosin cytoskeletal changes. In this study, we demonstrate the role of Yap/Taz-TEAD activity as a sensor of mechanical signals in the regulation of the progenitor behavior of boundary cells during zebrafish hindbrain compartmentalization. Monitoring of in vivo Yap/Taz activity during hindbrain segmentation indicated that boundary cells responded to mechanical cues in a cell-autonomous manner through Yap/Taz-TEAD activity. Cell-lineage analysis revealed that Yap/Taz-TEAD boundary cells decreased their proliferative activity when Yap/Taz-TEAD activity ceased, which preceded changes in their cell fate from proliferating progenitors to differentiated neurons. Functional experiments demonstrated the pivotal role of Yap/Taz-TEAD signaling in maintaining progenitor features in the hindbrain boundary cell population.


Subject(s)
Cell Division/genetics , DNA-Binding Proteins/physiology , Intracellular Signaling Peptides and Proteins/physiology , Nuclear Proteins/physiology , Rhombencephalon/cytology , Rhombencephalon/embryology , Stem Cells/physiology , Trans-Activators/physiology , Transcription Factors/physiology , Zebrafish Proteins/physiology , Animals , Animals, Genetically Modified , Body Patterning/genetics , Cell Differentiation/genetics , Cell Movement/genetics , DNA-Binding Proteins/genetics , Embryo, Nonmammalian , Intracellular Signaling Peptides and Proteins/genetics , Mechanical Phenomena , Mechanotransduction, Cellular/genetics , Mechanotransduction, Cellular/physiology , Neurogenesis/genetics , Nuclear Proteins/genetics , Organogenesis/genetics , Rhombencephalon/metabolism , Signal Transduction/genetics , Stem Cells/cytology , TEA Domain Transcription Factors , Trans-Activators/genetics , Transcription Factors/genetics , Transcriptional Coactivator with PDZ-Binding Motif Proteins , YAP-Signaling Proteins , Zebrafish/embryology , Zebrafish/genetics , Zebrafish Proteins/genetics
7.
Clin Kidney J ; 11(6): 841-845, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30524719

ABSTRACT

BACKGROUND: A good vascular access (VA) is vital for haemodialysis (HD) patients. HD with an autologous arteriovenous fistula (AVF) is associated with higher survival, lower health care costs and fewer complications. Although a distal forearm AVF is the best option, not all patients are good candidates for this approach and the primary failure rate ranges from 20% to 50%. The optimal AVF depends mainly on the anatomical and haemodynamic characteristics of the artery and the vein chosen for the anastomosis. These characteristics can be modified by performing physical exercise. VA guidelines suggest that isometric exercises should be performed both before and after the AVF is created. While the literature contains few data on the potential efficacy of preoperative exercise, small observational studies point to an improvement in venous and arterial calibre. Postoperative exercise also seems to improve maturation, although there is no consensus on the appropriate exercise protocol. METHODS: The PHYSICALFAV trial (NCT03213756) is an open-label, multicentre, prospective, controlled, randomized trial designed to evaluate the usefulness of preoperative isometric exercise (PIE) in pre-dialysis patients or in prevalent HD patients who are candidates for a new AVF. Patients are randomized 1:1 to the PIE group (isometric exercises for 8 weeks) or the control group (no exercise). The main endpoint is whether the rate of primary failure is lower in the PIE group than in the control group. RESULTS: The trial has already started, with 40 patients having been enrolled as of 21 March 2018; 26.5% of the estimated sample.

8.
Genetics ; 206(1): 231-249, 2017 05.
Article in English | MEDLINE | ID: mdl-28315837

ABSTRACT

Transforming Growth Factor ß (TGFß) signaling has a complex influence on cell proliferation, acting to stop cell division in differentiating cells, but also promoting cell division in immature cells. The activity of the pathway in Drosophila is mostly required to stimulate the proliferation of neural and epithelial tissues. Most interestingly, this function is not absolutely required for cell division, but it is needed for these tissues to reach their correct size. It is not known how TGFß signaling promotes cell division in imaginal discs, or what the interactions between TGFß activity and other signaling pathways regulating cell proliferation are. In this work, we have explored the disc autonomous function of TGFß that promotes wing imaginal disc growth. We have studied the genetic interactions between TGFß signaling and other pathways regulating wing disc growth, such as the Insulin and Hippo/Salvador/Warts pathways, as well as cell cycle regulators. We have also identified a collection of TGFß candidate target genes affecting imaginal growth using expression profiles. These candidates correspond to genes participating in the regulation of a variety of biochemical processes, including different aspects of cell metabolism, suggesting that TGFß could affect cell proliferation by regulating the metabolic fitness of imaginal cells.


Subject(s)
Cell Cycle Proteins/genetics , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Intracellular Signaling Peptides and Proteins/genetics , Protein Kinases/genetics , Protein Serine-Threonine Kinases/genetics , Transforming Growth Factor beta/genetics , Animals , Cell Division/genetics , Cell Proliferation/genetics , Cell Size , Drosophila melanogaster/growth & development , Gene Expression Regulation, Developmental , Genetic Fitness , Imaginal Discs/growth & development , Insulin/genetics , Signal Transduction , Transcriptome , Transforming Growth Factor beta/biosynthesis , Wings, Animal/growth & development
9.
Dev Biol ; 377(1): 138-53, 2013 May 01.
Article in English | MEDLINE | ID: mdl-23485686

ABSTRACT

The development of the Drosophila wing disc requires the activities of the BMP and TGFß signalling pathways. BMP signalling is critical for the correct growth and patterning of the disc, whereas the related TGFß pathway is mostly required for growth. The BMP and TGFß pathways share a common co-receptor (Punt) and a nuclear effector (Medea), and consequently it is likely that these pathways can interfere with each other during normal development. In this work we focus on the spatial activation domains and requirements for TGFß signalling during wing disc development. We found that the phosphorylation of Smad2, the specific transducer for TGFß signalling, occurs in a generalised manner in the wing disc. It appears that the expression of the four candidate TGFß ligands (Activinß, Dawdle, Maverick and Myoglianin) in the wing disc is required to obtain normal levels of TGFß signalling in this tissue. We show that Baboon, the specific receptor of the TGFß pathway, can phosphorylate Mad, the specific transducer of the BMP pathway, in vivo. However, this activation only occurs in the wing disc when the receptor is constitutively activated in a background of reduced expression of Smad2. In the presence of Smad2, the normal situation during wing disc development, high levels of activated Baboon lead to a depletion in Mad phosphorylation and to BMP loss-of-function phenotypes. Although loss of either babo or Smad2 expression reduce growth in the wing blade in a similar manner, loss of Smad2 can also cause phenotypes related to ectopic BMP signalling, suggesting a physiological role for this transducer in the regulation of Mad spatial activation.


Subject(s)
Bone Morphogenetic Proteins/metabolism , Drosophila melanogaster/growth & development , Drosophila melanogaster/metabolism , Signal Transduction , Transforming Growth Factor beta/metabolism , Wings, Animal/growth & development , Wings, Animal/metabolism , Animals , Cell Death , Cell Proliferation , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/cytology , Drosophila melanogaster/genetics , Female , Gene Expression Regulation, Developmental , Imaginal Discs/cytology , Imaginal Discs/metabolism , Ligands , Mutation/genetics , Organ Size , Phenotype , RNA Interference , Signal Transduction/genetics , Wings, Animal/anatomy & histology , Wings, Animal/cytology
11.
Perit Dial Int ; 28(2): 118-22, 2008.
Article in English | MEDLINE | ID: mdl-18332443

ABSTRACT

The treatment of cirrhotic patients with ascites and end-stage renal disease is complex, due mainly to decreased effective arterial volume and hemodynamic instability. Peritoneal dialysis as a continuous therapy represents an alternative to hemodialysis-related intolerance. We report on our experience and that of others with cirrhotic patients with ascites treated by peritoneal dialysis. Hemodynamic tolerance was excellent in all patients and solute and water peritoneal transport increased to above the normal range in almost all cases. Morbidity and mortality were related principally to liver disease and other comorbidities. Peritoneal protein losses, initially high, decreased over time, maintaining serum albumin within the low normal range. The incidence of peritonitis was similar or slightly higher than usual in these patients, with peculiar etiology. The experiences with peritoneal dialysis suggest consideration of this treatment as the first choice for cirrhotic patients with ascites and that need to start dialysis.


Subject(s)
Ascites/complications , Kidney Failure, Chronic/therapy , Liver Cirrhosis/complications , Peritoneal Dialysis , Adult , Catheters, Indwelling , Humans , Kidney Failure, Chronic/complications , Male , Nutritional Status , Peritoneal Dialysis/adverse effects , Peritoneal Dialysis, Continuous Ambulatory , Peritonitis/etiology , Peritonitis/therapy
12.
J Nephrol ; 20(5): 626-8, 2007.
Article in English | MEDLINE | ID: mdl-17918150

ABSTRACT

Glomerulonephritis rarely appears associated with Hodgkin's disease or non-Hodgkin's lymphoma (NHL). We present a patient with a relapse of a non-Hodgkin's lymphoma which first presented as nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS). This case report discusses the unusual association of non-Hodgkin's lymphoma and focal segmental glomerulosclerosis, as well as the crucial role of positron emission tomography in detecting the relapsing lymphoma.


Subject(s)
Glomerulosclerosis, Focal Segmental/complications , Lymphoma, Non-Hodgkin/diagnostic imaging , Nephrotic Syndrome/etiology , Positron-Emission Tomography , Aged , Glomerulosclerosis, Focal Segmental/diagnostic imaging , Glomerulosclerosis, Focal Segmental/etiology , Glomerulosclerosis, Focal Segmental/pathology , Humans , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/pathology , Male , Nephrotic Syndrome/diagnostic imaging , Nephrotic Syndrome/pathology , Recurrence
13.
Nephrol Dial Transplant ; 22(1): 218-23, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17005522

ABSTRACT

BACKGROUND: High peritoneal transport has been associated with poorer outcome in peritoneal dialysis (PD) patients, but not necessarily because of PD-dependent conditions. Our primary objective was to analyse the influences of baseline peritoneal small solute transport and ultrafiltration (UF) capacity on patient and technique survival, after adjusting for comorbid conditions. A secondary objective was to determine whether high transport was associated with basal comorbidity. METHODS: In this prospective observational patient/technique survival study, we followed 410 patients who started PD. At the baseline, we collected data to define comorbidities, tally the Charlson index, determine the baseline mass transfer area coefficients (MTAC) of urea and creatinine, net UF, plasma albumin and residual renal function (RRF). No data other than the information on patient and technique survival were recorded after baseline. RESULTS: The mean follow-up was 33 +/- 28 months. Dropouts during the study were due to renal transplantation in 140 cases, death in 142 cases and transfer to haemodialysis (HD) in 77 cases. Patients with inherent UF deficiency, high transport rate or both were not significantly different in the survival analysis from the rest. In the Cox hazards analysis, only age, Charlson index and a lower RRF were the significant mortality risk factors. None of the baseline parameters studied was a predictor of technique failure. High transporter patients had lower plasma albumin and UF capacity, comorbidity and more frequent liver diseases than the rest. Moderate to severe liver disease (n = 14) was significantly associated with the inherent high transport status, but was never accompanied by UF failure (UFF). UFF patients showed higher RRF, creatinine-MTAC and age. CONCLUSIONS: Neither the high transport nor the inherent UFF status has any influence on patient and technique survival. The inherent high small solute transport status is associated with hypoalbuminaemia and a greater comorbidity index. The Charlson index, age and lower RRF are the only independent predictors of mortality. Technique dropout is not predicted by any of the variables studied at the baseline.


Subject(s)
Peritoneal Dialysis, Continuous Ambulatory/methods , Ultrafiltration/methods , Aged , Comorbidity , Female , Follow-Up Studies , Humans , Kidney/pathology , Liver Diseases/pathology , Male , Middle Aged , Peritoneum/metabolism , Proportional Hazards Models , Prospective Studies , Treatment Outcome
14.
Adv Perit Dial ; 22: 77-81, 2006.
Article in English | MEDLINE | ID: mdl-16983945

ABSTRACT

Fungal peritonitis (FP) is an infrequent cause of peritonitis in peritoneal dialysis (PD), but it has high morbidity and mortality. We analyzed the experience with FP in a single PD unit over a 24-year period. We identified 671 episodes of peritonitis that occurred in 496 patients during the study period. Of these episodes, 23 (3.4%) were FP episodes occurring in 21 patients. In the FP episodes, the patients' mean time on PD was 29.2 +/- 27 months. In 5 episodes, the patients had experienced a peritonitis episode within the preceding month, and in 11 episodes, the patients had used antibiotics within the preceding month. The FP diagnosis was made a mean of 3.17 +/- 3 days after the diagnosis of peritonitis, and in 1 patient, the diagnosis was made after death. Candida spp. were isolated in 82.6% of patients. In 91.3%, the peritoneal catheter was removed. After the FP diagnosis, 15 patients dropped out of PD, but in only 8 patients (34.7%) was drop-out related to FP. In 4 patients, drop-out occurred because of peritoneal membrane failure, and 4 patients (17.4%) died. Time on PD was significantly higher in the group of patients that dropped out of PD because of the FP (45.7 +/- 31 months vs. 19 +/- 18 months, p = 0.02). Fungal peritonitis is a rare cause of peritonitis in PD patients, but it is associated with high morbidity and mortality. Longer time on PD is the main factor in technique failure and mortality.


Subject(s)
Mycoses/etiology , Peritoneal Dialysis/adverse effects , Peritonitis/etiology , Antifungal Agents/therapeutic use , Female , Humans , Male , Middle Aged , Mycoses/microbiology , Mycoses/mortality , Mycoses/therapy , Peritonitis/microbiology , Peritonitis/mortality , Peritonitis/therapy , Survival Analysis , Survival Rate
15.
Nephrol Dial Transplant ; 20(6): 1201-6, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15827050

ABSTRACT

BACKGROUND: Studies on the evolution of peritoneal transport during the first year of peritoneal dialysis (PD) are scarce and their results are contradictory. The aim of the present study was to analyse the evolution of peritoneal transport and residual renal function during the first year on PD, and to determine the factors that may influence them. METHODS: We studied 249 patients on continuous ambulatory PD with glucose exchange solutions (117 men, 132 women, mean age 51.9+/-16 years) 59 of whom had diabetes (25 type I). At baseline and after 1 year, we determined the mass transfer coefficients of urea (U-MTAC) and creatinine (Cr-MTAC), net ultrafiltration and residual renal function. RESULTS: Residual renal function decreased significantly during the first year (from 3.9+/-2.8 to 2.4+/-2.2 ml/min, P<0.001). Both U-MTAC and Cr-MTAC decreased after 1 year [U-MTAC from 22.7+/-7.8 to 20.7+/-6.6 ml/min (P<0.001), Cr-MTAC from 10.5+/-5.3 to 10.1+/-4.6 ml/min (NS)]. The ultrafiltration capacity increased significantly (from 923+/-359 to 987 U 341 ml/4 h, P<0.001). The evolution of MTAC values was independent of age, sex, diabetes and amount of hypertonic glucose used. When patients were grouped according to their initial Cr-MTAC, we observed a tendency toward normalization of the parameters of peritoneal function. Patients with peritonitis (n = 88) showed a first year increase in Cr-MTAC, which was significantly higher than in patients without peritonitis (11.1+/-5 vs 9.5+/-4.2, P<0.01). Ultrafiltration decreased in patients with more than four accumulated days of peritonitis (from 1062+/-447 to 1024+/-340 ml/4 h, NS); it increased in patients without peritonitis. CONCLUSIONS: The peritoneal transport parameters tended toward normalization during the first year on PD, mainly with a decrease of small solute transport and an increase of ultrafiltration capacity. This evolution is independent of age, gender, diabetes and higher exposure to glucose in PD solutions. Peritonitis was the only independent factor that affected peritoneal function during the first year on peritoneal dialysis.


Subject(s)
Peritoneal Dialysis, Continuous Ambulatory , Peritoneum/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Biological Transport , Child , Creatinine , Female , Humans , Kidney Function Tests , Male , Middle Aged , Peritonitis/epidemiology , Peritonitis/physiopathology , Ultrafiltration , Urea
16.
Perit Dial Int ; 25(1): 68-76, 2005.
Article in English | MEDLINE | ID: mdl-15770928

ABSTRACT

BACKGROUND: Human peritoneal function on commencing peritoneal dialysis (PD) is not yet adequately understood. The objective of this study was to determine peritoneal functional patterns on commencing PD. METHODS: 367 end-stage renal disease (ESRD) patients on PD for the first time were studied between their initial second to sixth weeks on PD. Urea and creatinine mass transfer area coefficients (MTAC) and standardized ultrafiltration (UF) capacity were determined. RESULTS: Mean parametric values were MTAC urea 22.9 +/- 7.04 mL/min, MTAC creatinine 10.31 +/- 4.68 mL/min, and UF 896 +/- 344 mL. Gender, patient size, and diabetes or kidney disease did not affect these parameters. The relationship between values of MTAC creatinine and UF reached statistical significance, although with a low value for Pearson's coefficient (r = -0.30, p = 0.001). Age showed a significant inverse linear correlation with UF capacity (r = -0.15, p = 0.003) and MTAC urea (r = -0.11, p < 0.05). Logistic regression analysis demonstrated that UF below 400 mL was independently related to a high MTAC creatinine and older age. Diabetes was least frequent in patients with the lowest UF. However, in the analysis of MTAC creatinine quintiles, UF values did not follow the expected inverse pattern. The lack of differences in UF between the second and third to fourth MTAC creatinine quintiles is remarkable; MTAC creatinine ranged from 6.71 to 13.54. CONCLUSIONS: The functional characteristics of human peritoneum varied markedly and there was a less intense than expected relationship between solute and water transports. This mild inverse relationship is intriguing and suggestive of the necessity of redefining some basic concepts. Age was associated with a lower peritoneal UF capacity, in part independently of small solute transport.


Subject(s)
Dialysis Solutions/pharmacokinetics , Kidney Failure, Chronic/metabolism , Peritoneal Dialysis , Peritoneum/metabolism , Adult , Aged , Biological Transport , Creatinine/metabolism , Female , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Retrospective Studies , Ultrafiltration , Urea/metabolism
17.
Adv Perit Dial ; 20: 209-12, 2004.
Article in English | MEDLINE | ID: mdl-15384828

ABSTRACT

Anorexia and malnutrition are common complications and powerful predictors of morbidity and mortality in peritoneal dialysis (PD) patients. Megestrol acetate (MA) is a progestogen that has been demonstrated to increase appetite and weight in patients with cancer or acquired immunodeficiency syndrome. To determine whether MA might benefit PD patients, we treated 32 patients with 160 mg MA daily. Treatment lasted a mean of 5.93 +/- 5.12 months (range: 1 - 23 months). In 68.8% of the patients, appetite improved. Weight gain was statistically significant starting in the third month (initial weight: 66.5 +/- 11.4 kg; weight at third month: 68 +/- 10.4 kg; p < 0.05). We observed a nonsignificant increase in serum albumin at the third treatment month (initial serum albumin: 3.44 +/- 0.27 g/L; serum albumin at third month: 3.54 +/- 0.27 g/L; p = 0.45). No side effects were observed. Our experience suggests that treatment with 160 mg MA daily in PD patients leads to an increase in appetite, serum albumin, and weight gain in most patients, with no negative side effects.


Subject(s)
Anorexia/drug therapy , Malnutrition/drug therapy , Megestrol Acetate/therapeutic use , Peritoneal Dialysis , Anorexia/etiology , Appetite/drug effects , Female , Humans , Male , Malnutrition/etiology , Middle Aged , Serum Albumin/analysis , Weight Gain
18.
Perit Dial Int ; 23(3): 249-54, 2003.
Article in English | MEDLINE | ID: mdl-12938825

ABSTRACT

BACKGROUND: Patients treated with peritoneal dialysis (PD) have increased intra-abdominal pressure and a high prevalence of abdominal wall complications. OBJECTIVE: The purpose of this study was to determine the incidence of hernias and peritoneal leaks in our PD patients and to investigate their potential risk factors. PATIENTS: We studied 142 unselected patients treated with PD during the past 5 years, including those that were already on PD and those that started PD during this period. Mean age was 54 years and mean follow-up on PD was 39 months. 72 patients had been treated with only continuous ambulatory PD (CAPD), 8 with automated PD (APD), and 62 with both modalities. RESULTS: 53 patients (37%) developed hernia and/or leak. A total of 39 hernias and 63 leaks were registered. The overall rates were 0.08 hernias/patient/year and 0.13 leaks/patient/year. 17 patients had both abdominal complications. Hernia was most frequently located in the umbilical region, and the most frequent site of leakage was the pericatheter area. Both complications appeared more frequently during the CAPD period (87% of hernias, 81% of leaks). The rate of hernias was higher in patients treated only with CAPD than in those that used only cyclers [0.08 vs 0.01 hernias/patient/year, not significant (NS)]. No patient treated only with APD had peritoneal leak; 25% (18/72) of patients treated with CAPD developed this complication (p = 0.18, NS). Dialysate exchange volumes ranged from 2000 to 2800 mL. 25 (66%) patients required surgical repair of the hernia, with recurrence in 7 patients (28%). 27 (84%) patients with leaks were initially treated with transitory temporary transfer to hemodialysis, low volume APD, or intermittent PD for 4 weeks. The leak recurred in half of the cases and surgical repair was necessary in 12 cases. The development of hernia and/or leak did not correlate with gender, diabetes, duration of follow-up, type of PD, history of abdominal surgery, or with the largest peritoneal exchange volume used. Polycystic kidney disease was the only factor associated with higher rate of hernias (p = 0.005), whereas increased age (p = 0.04) and higher body mass index (p = 0.03) were significantly associated with the appearance of leaks. CONCLUSION: Abdominal hernias and peritoneal leaks are very frequent in the PD population. Advanced age, polycystic kidney disease, and high body mass index are independent risk factors for their development. Automated PD with low daytime fill volume should be considered in all patients at risk for hernias and/or leaks.


Subject(s)
Hernia, Ventral/etiology , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/adverse effects , Peritoneal Diseases/etiology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hernia, Ventral/epidemiology , Hernia, Ventral/therapy , Humans , Incidence , Male , Middle Aged , Peritoneal Diseases/epidemiology , Peritoneal Diseases/therapy , Risk Factors , Treatment Outcome
19.
Hemodial Int ; 5(1): 55-58, 2001 Jan.
Article in English | MEDLINE | ID: mdl-28452446

ABSTRACT

In dialysis patients, C-reactive protein (CRP), a well-recognized marker of inflammation, predicts mortality. Higher levels have been described in hemodialysis (HD) patients as compared with peritoneal dialysis (PD) patients. Our aim was to determine, based on CRP plasma levels, the degree of inflammation in HD patients using low-permeability polysulfone membranes and relatively pure dialysate, and that in PD patients. A secondary objective was to study factors associated with hypoalbuminemia and inflammation in both populations. We studied 69 stable patients on dialysis (32 on HD and 37 on PD). The mean age was 69.9 ± 8.2 years, and the mean time on dialysis was 27 months. The two populations were comparable for overall and cardiovascular comorbidities. Nephelometry was used to measure CRP plasma levels (normal levels < 0.6 mg/dL). The Kt/Vurea , corrected for residual renal clearance, and the equivalent of protein nitrogen appearance (PNA) were also calculated. Of the patients studied, 53% showed CRP plasma levels higher than 0.6 mg/dL; in 36%, the levels were higher than 1 mg/dL. No significant differences in these percentages were noted between the two dialysis groups. Patients with CRP levels higher than 1 mg/dL showed lower serum albumin, iron, hemoglobin, and transferrin levels, and higher ferritin values and leukocyte counts. Under logistic regression analysis, CRP levels higher and lower than 1 mg/dL were significantly associated with serum albumin [p = 0.01; odds ratio (OR): 0.15], iron (p = 0.006; OR: 0.96), transferrin (p = 0.004; OR: 0.97), and hemoglobin (p = 0.02; OR: 0.67). Serum albumin levels were significantly lower in PD patients. Under regression analysis, serum albumin levels correlated with cholesterol (r: 0.25; p = 0.04), serum iron (r: 0.5; p = 0.0001), transferrin (r: 0.3; p = 0.015), ultrafiltration capacity (r: 0.42; p = 0.008), and CRP values above 0.6 mg/dL (r: -0.65; p = 0.001). In conclusion, the frequent elevation of CRP plasma levels observed in both HD and PD patients suggests the presence of a silent inflammatory state. Hemodialysis performed with biocompatible, low-permeability membranes is not associated with higher CRP plasma levels than those seen in PD. In both groups, hypoalbuminemia is related to CRP level. Levels of serum albumin, slightly lower in PD patients, are also related to peritoneal ultrafiltration capacity.

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