Hypermethylation-Mediated Silencing of CIDEA, MAL and PCDH17 Tumour Suppressor Genes in Canine DLBCL: From Multi-Omics Analyses to Mechanistic Studies.

Gene expression is controlled by epigenetic deregulation, a hallmark of cancer. The DNA methylome of canine diffuse large B-cell lymphoma (cDLBCL), the most frequent malignancy of B-lymphocytes in dog, has recently been investigated, suggesting that aberrant hypermethylation of CpG loci is associated with gene silencing. Here, we used a multi-omics approach (DNA methylome, transcriptome and copy number variations) combined with functional in vitro assays, to identify putative tumour suppressor genes subjected to DNA methylation in cDLBCL. Using four cDLBCL primary cell cultures and CLBL-1 cells, we found that CiDEA, MAL and PCDH17, which were significantly suppressed in DLBCL samples, were hypermethylated and also responsive (at the DNA, mRNA and protein level) to pharmacological unmasking with hypomethylating drugs and histone deacetylase inhibitors. The regulatory mechanism underneath the methylation-dependent inhibition of those target genes expression was then investigated through luciferase and in vitro methylation assays. In the most responsive CpG-rich regions, an in silico analysis allowed the prediction of putative transcription factor binding sites influenced by DNA methylation. Interestingly, regulatory elements for AP2, MZF1, NF-kB, PAX5 and SP1 were commonly identified in all three genes. This study provides a foundation for characterisation and experimental validation of novel epigenetically-dysregulated pathways in cDLBCL.

G-Quadruplex Modulation of SP1 Functional Binding Sites at the KIT Proximal Promoter.

The regulation of conformational arrangements of gene promoters is a physiological mechanism that has been associated with the fine control of gene expression. Indeed, it can drive the time and the location for the selective recruitment of proteins of the transcriptional machinery. Here, we address this issue at the KIT proximal promoter where three G-quadruplex forming sites are present (kit1, kit2 and kit*). On this model, we focused on the interplay between G-quadruplex (G4) formation and SP1 recruitment. By site directed mutagenesis, we prepared a library of plasmids containing mutated sequences of the WT KIT promoter that systematically exploited different G4 formation attitudes and SP1 binding properties. Our transfection data showed that the three different G4 sites of the KIT promoter impact on SP1 binding and protein expression at different levels. Notably, kit2 and kit* structural features represent an on-off system for KIT expression through the recruitment of transcription factors. The use of two G4 binders further helps to address kit2-kit* as a reliable target for pharmacological intervention.

Targeting Canine KIT Promoter by Candidate DNA G-Quadruplex Ligands.

G-quadruplexes (G4) are nucleic acid secondary structures frequently assumed by G-rich sequences located mostly at telomeres and proto-oncogenes promoters. Recently, we identified, in canine KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) promoter, two G-rich sequences able to fold into G4: d_kit1 and d_kit2_A16. In this study, an anthraquinone (AQ1) and an anthracene derivative (AN6), known to stabilize the G4 structures of the corresponding human h_kit1 and h_kit2, were tested on the canine G4 and in two canine mast cell tumor (MCT) cell lines (C2 and NI-1) to verify their capability to down-regulate KIT expression. The cytotoxicity of AQ1 and AN6 was determined using the Alamar Blue test; also the constitutive expression of KIT and other proto-oncogenes containing G4 structures in their promoter (BCL2, VEGFα, VEGFR2, KRAS, and TERT) was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Then the time- and dose-dependent effects of both ligands on target gene expression were assessed by qRT-PCR. All target genes were constitutively expressed up to 96 hours of culture. Both ligands decreased KIT mRNA levels and c-kit protein amount, and AN6 was comparatively fairly more effective. DNA interaction studies and a dual-luciferase gene reporter assay performed on a noncancerous canine cell line (Madin-Darby Canine Kidney cells) proved that this down-regulation was the result of the interaction of AN6 with KIT proximal promoter. Interestingly, our results only partially overlap with those previously obtained in human cell lines, where AQ1 was found as the most effective compound. These preliminary data might suggest AN6 as a promising candidate for the selective targeting of canine KIT-dependent tumors.

Mortality in Elderly Waiting-List Patients Versus Age-Matched Kidney Transplant Recipients: Where is the Risk?

The number of elderly patients on the waiting list (WL) for kidney transplantation (KT) has risen significantly in recent years. Because KT offers a better survival than dialysis therapy, even in the elderly, candidates for KT should be selected carefully, particularly in older waitlisted patients. Identification of risk factors for death in WL patients and prediction of both perioperative risk and long-term post-transplant mortality are crucial for the proper allocation of organs and the clinical management of these patients in order to decrease mortality, both while on the WL and after KT. In this review, we examine the clinical results in studies concerning: a) risk factors for mortality in WL patients and KT recipients; 2) the benefits and risks of performing KT in the elderly, comparing survival between patients on the WL and KT recipients; and 3) clinical tools that should be used to assess the perioperative risk of mortality and predict long-term post-transplant survival. The acknowledgment of these concerns could contribute to better management of high-risk patients and prophylactic interventions to prolong survival in this particular population, provided a higher mortality is assumed.

Indenocinnoline derivatives as G-quadruplex binders, topoisomerase IIα inhibitors and antiproliferative agents.

DNA intercalating agents are a consolidated therapeutic option in the treatment of tumor diseases. Starting from previous findings in the antiproliferative efficacy of a series of indeno[1,2-c]cinnoline-11-one derivatives, we performed a suitable decoration of this scaffold by means of a simple and straightforward chemistry, aiming to a) enlarge the planar core to a pentacyclic benzo[h]indeno[1,2-c]cinnoline-13-one and b) introduce a basic head tethered through a simple polymethylene chain. In fluorescence melting and fluorescence intercalator displacement assays, these new compounds displayed fair to very good intercalating properties on different nucleic acid strands, with preference for G-quadruplex sequences. Inhibition of human topoisomerase IIα and antiproliferative assays on HeLa and MCF7 tumor cell lines outlined a multitarget antiproliferative profile for tetracyclic 6 and pentacyclic derivative 20, both bearing a N,N-dimethylamine as the protonatable moiety. Particularly, compound 6 displayed a very potent inhibition of tumor cell proliferation, while 20 returned the highest thermal stabilization in melting experiments. In summary, these results outlined a potential of such highly planar scaffolds for nucleic acid binding and antiproliferative effects.

Development and Validation of the Acute PNeumonia Early Assessment Score for Safely Discharging Low-Risk SARS-CoV-2-Infected Patients from the Emergency Department.

A continuous demand for assistance and an overcrowded emergency department (ED) require early and safe discharge of low-risk severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. We developed (n = 128) and validated (n = 330) the acute PNeumonia early assessment (aPNea) score in a tertiary hospital and preliminarily tested the score on an external secondary hospital (n = 97). The score's performance was compared to that of the National Early Warning Score 2 (NEWS2). The composite outcome of either death or oral intubation within 30 days from admission occurred in 101 and 28 patients in the two hospitals, respectively. The area under the receiver operating characteristic (AUROC) curve of the aPNea model was 0.86 (95% confidence interval (CI), 0.78-0.93) and 0.79 (95% CI, 0.73-0.89) for the development and validation cohorts, respectively. The aPNea score discriminated low-risk patients better than NEWS2 at a 10% outcome probability, corresponding to five cut-off points and one cut-off point, respectively. aPNea's cut-off reduced the number of unnecessary hospitalizations without missing outcomes by 27% (95% CI, 9-41) in the validation cohort. NEWS2 was not significant. In the external cohort, aPNea's cut-off had 93% sensitivity (95% CI, 83-102) and a 94% negative predictive value (95% CI, 87-102). In conclusion, the aPNea score appears to be appropriate for discharging low-risk SARS-CoV-2-infected patients from the ED.

Epidemiology of amyotrophic lateral sclerosis in Friuli-Venezia Giulia, North-Eastern Italy, 2002-2014: a retrospective population-based study.

OBJECTIVES: To describe the epidemiology of Amyotrophic Lateral Sclerosis (ALS) in Friuli-Venezia Giulia (FVG) region, Italy, over a 13-year period (2002-2014), estimating ALS (a) incidence, prevalence, and clinical features; (b) mortality, also comparing Udine municipality to the rest of FVG. METHODS: We conducted a retrospective population-based study. ALS incident cases were ascertained using multiple sources and validated through expert review. We calculated crude and standardized incidence rate (IR), point prevalence and mortality rate (MR), each with 95% confidence interval. Standardized incidence (SIR) and mortality (SMR) ratio were calculated to compare Udine to FVG. RESULTS: Among 444 incident cases (50.0% men, median age 68.5 years), onset was bulbar in 30.2%, spinal in 59.9%, mixed in 9.9%; 3.6% had familial ALS. Crude and 2000 European population standardized IR was respectively 2.81 (2.56-3.09) and 2.09 (1.89-2.29) per 100,000 person-years. Standardized male-to-female incidence ratio was 1.05. IR peaked at age 65-74 years (men: 9.93, 8.04-12.32; women: 7.74, 6.18-9.67) and decreased thereafter. Prevalence was 8.36 (6.74-9.97) cases per 100,000 inhabitants on 30 June 2009 and 7.98 (6.40-9.56) on 30 June 2014. SIR was 1.20 and SMR 1.11. CONCLUSIONS: When assessed over a long period, incidence of ALS was in the range of Italian and European population-based registries and showed a consistent pattern by age and sex. IR and MR were only slightly higher in Udine vs. FVG.

DNA elements for constitutive androstane receptor- and pregnane X receptor-mediated regulation of bovine CYP3A28 gene.

The regulation of cytochrome P450 3A (CYP3A) enzymes is established in humans, but molecular mechanisms of its basal and xenobiotic-mediated regulation in cattle are still unknown. Here, ~10 kbp of the bovine CYP3A28 gene promoter were cloned and sequenced, and putative transcription factor binding sites were predicted. The CYP3A28 proximal promoter (PP; -284/+71 bp) contained DNA elements conserved among species. Co-transfection of bovine nuclear receptors (NRs) pregnane X and constitutive androstane receptor (bPXR and bCAR) with various CYP3A28 promoter constructs into hepatoma cell lines identified two main regions, the PP and the distal fragment F3 (-6899/-4937 bp), that were responsive to bPXR (both) and bCAR (F3 fragment only). Site-directed mutagenesis and deletion of NR motif ER6, hepatocyte nuclear factor 1 (HNF-1) and HNF-4 binding sites in the PP suggested either the involvement of ER6 element in bPXR-mediated activation or the cooperation between bPXR and liver-enriched transcription factors (LETFs) in PP transactivation. A putative DR5 element within the F3 fragment was involved in bCAR-mediated PP+F3 transactivation. Although DNA enrichment by anti-human NR antibodies was quite low, ChIP investigations in control and RU486-treated BFH12 cells, suggested that retinoid X receptor α (RXRα) bound to ER6 and DR5 motifs and its recruitment was enhanced by RU486 treatment. The DR5 element seemed to be recognized mainly by bCAR, while no clear-cut results were obtained for bPXR. Present results point to species-differences in CYP3A regulation and the complexity of bovine CYP3A28 regulatory elements, but further confirmatory studies are needed.

Validation of epigenetic mechanisms regulating gene expression in canine B-cell lymphoma: An in vitro and in vivo approach.

Despite canine B-cell Lymphoma (BCL) representing the most common haematological tumour, epigenetic events driving development and progression are scarcely known. Recently, canine Diffuse Large BCL (DLBCL) DNA methylome by genome-wide CpG microarray has identified genes and pathways associated to pathogenesis. To validate data previously obtained by array analysis, the CLBL-1 cell line was used and the HOXD10, FGFR2, ITIH5 and RASAL3 genes were selected. CLBL-1 cells were treated with two hypomethylating drugs (HDs; IC50, 50% inhibitory concentration), i.e. azacytidine and decitabine (DEC), either alone or in combination with three histone deacetylase inhibitors (HDACis; IC20), i.e. valproic acid, trichostatin and vorinostat. Following the incubation with both HDs, an overall decrease of promoter methylation was highlighted, thus confirming target genes hypermethylation. The highest mRNA restoration was observed following the exposure to HDs combined with HDACis, and mostly with valproic acid. Contrasting results were only obtained for RASAL3. An in vivo confirmation was finally attempted treating Nod-Scid mice engrafted with CLBL-1 cells with DEC. Although DEC did not arrest tumour growth, target genes promoter methylation was significantly reduced in DEC-treated mice vs controls. Overall, this work demonstrates that CLBL-1 cell line represents a reliable in vitro model to validate the methylation-dependent silencing of key genes for BCL; moreover, it may be useful for xenograft models in mice, despite its aggressive behaviour. In future, functional studies will be performed to deepen the role of selected genes on BCL pathogenesis and progression, and their methylation-dependent mechanism of regulation.

In Silico Identification of Piperidinyl-amine Derivatives as Novel Dual Binders of Oncogene c-myc/c-Kit G-quadruplexes.

In the last years, it has been shown that the DNA secondary structure known as G-quadruplex is also involved in the regulation of oncogenes transcription, such as c-myc, c-Kit, KRAS, Bcl-2, VEGF, and PDGF. DNA G-quadruplexes, formed in the promoter region of these proto-oncogenes, are considered alternative anticancer targets since their stabilization causes a reduction of the related oncoprotein overexpression. In this study, a structure-based virtual screening toward the experimental DNA G-quadruplex structures of c-myc and c-Kit was performed by using Glide for the docking analysis of a commercial library of approximately 693 000 compounds. The best hits were submitted to thermodynamic and biophysical studies, highlighting the effective stabilization of both G-quadruplex oncogene promoter structures for three N-(4-piperidinylmethyl)amine derivatives, thus proposed as a new class of dual G-quadruplex binders.

Cystatin C as marker of residual renal function in patients on peritoneal dialysis: relation with parameters of peritoneal function.

INTRODUCTION: Cystatin C (CysC) is a nonglycosylated protein of low molecular weight not influenced by age, sex or inflammation. The aim of this paper is to ascertain the usefulness of serum CysC level determination in peritoneal dialysis (PD) patients. MATERIAL AND METHODS: CysC serum levels were determined in 80 PD patients. The mean age of patients was 53.7 +/- 15 years, with 15.3 +/- 25.8 months on PD. Thirty-three percent were on continuous ambulatory peritoneal dialysis (CAPD) and 66.3% on automated peritoneal dialysis (APD). Fourteen patients (17%) had no residual renal function (RRF). RESULTS: Mean CysC levels were 5.8 +/- 1.4 mg/L, without differences between men (5.5 +/- 1.4 mg/L) and women (5.6 +/- 1.5 mg/L, NS). There was no correlation between CysC levels and age, weight, height or time on PD. Anuric patients had CysC levels significantly higher than non-anuric (6.7 +/- 1.4 vs. 5.3 +/- 1.3 mg/L, p<0.001). CysC levels showed an inverse correlation with RRF (r=-0.60, p<0.001) and residual urine volume (r=-0.58, p<0.001). CONCLUSIONS: In conclusion, serum CysC levels had the same statistical significance as plasma creatinine levels, and they are not influenced by peritoneal transport in PD patients. Consequently, both parameters are valid RRF markers.

DNA methylation profiling reveals common signatures of tumorigenesis and defines epigenetic prognostic subtypes of canine Diffuse Large B-cell Lymphoma.

Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5'-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern. Functional analysis highlighted biological processes strongly related to embryonic development, tissue morphogenesis and cellular differentiation, including HOX, BMP and WNT. In addition, the analysis of epigenetic patterns and genome-wide methylation variability identified cDLBCL subgroups. Some of these epigenetic subtypes showed a concordance with the clinical outcome supporting the hypothesis that the accumulation of aberrant epigenetic changes results in a more aggressive behavior of the tumor. Collectively, our results suggest an important role of DNA methylation in DLBCL where aberrancies in transcription factors were frequently observed, suggesting an involvement during tumorigenesis. These findings warrant further investigation to improve cDLBCL prognostic classification and provide new insights on tumor aggressiveness.

Peritoneal transport in peritoneal dialysis patients is not affected by transitorily successful renal transplantation.

Patients returning to peritoneal dialysis (PD) from failed renal transplantation are recognized to be inflamed, and this situation might produce a high peritoneal solute transport status. We wanted to determine if a period of time with a kidney allograft induces a change in peritoneal function. We studied 19 PD patients who had been living with a graft for a mean of 47 +/- 39 months. We studied their peritoneal function upon starting PD (baseline), immediately before transplantation (pre-Tx), and after returning to PD when the graft failed (post-Tx). We analyzed the peritoneal mass transfer coefficients for urea (U-MTAC) and creatinine (Cr-MTAC), the dialysate-to-plasma ratio of creatinine (D/P-Cr), and net ultrafiltration (UF). We observed no significant differences in the various variables pre-Tx and post-Tx. The U-MTAC post-Tx was significantly lower than at PD baseline (25.9 +/- 8 mL/min vs. 20.2 +/- 5 mL/min, p = 0.03). The U-MTAC and Cr-MTAC post-Tx were not correlated with months on a graft or with MTAC values at baseline. In inherent high transporters (Cr-MTAC > or = 11.5 mL/min at baseline, n = 8), we observed a significant reduction in Cr-MTAC post-Tx (15.2 +/- 2 mL/min vs. 10.2 +/- 4 mL/min, p = 0.03). Three of these patients remained high transporters post-Tx. We conclude that peritoneal function upon reinitiating PD after transplantation is similar to function in the pre-transplantation phase; and that a high peritoneal transport status is more prevalent at first initiation onto PD than at return after transplantation, suggesting that inherently high transport is almost exclusively a feature of an intact, predialysis peritoneum.

Screening of candidate G-quadruplex ligands for the human c-KIT promotorial region and their effects in multiple in-vitro models.

Stabilization of G-quadruplex (G4) structures in promoters is a novel promising strategy to regulate gene expression at transcriptional and translational levels. c-KIT proto-oncogene encodes for a tyrosine kinase receptor. It is involved in several physiological processes, but it is also dysregulated in many diseases, including cancer. Two G-rich sequences able to fold into G4, have been identified in c-KIT proximal promoter, thus representing suitable targets for anticancer intervention. Herein, we screened an "in house" library of compounds for the recognition of these G4 elements and we identified three promising ligands. Their G4-binding properties were analyzed and related to their antiproliferative, transcriptional and post-transcriptional effects in MCF7 and HGC27 cell lines. Besides c-KIT, the transcriptional analysis covered a panel of oncogenes known to possess G4 in their promoters.From these studies, an anthraquinone derivative (AQ1) was found to efficiently downregulate c-KIT mRNA and protein in both cell lines. The targeted activity of AQ1 was confirmed using c-KIT-dependent cell lines that present either c-KIT mutations or promoter engineered (i.e., α155, HMC1.2 and ROSA cells).Present results indicate AQ1 as a promising compound for the target therapy of c-KIT-dependent tumors, worth of further and in depth molecular investigations.

Treatment of anorexia and malnutrition in peritoneal dialysis patients with megestrol acetate.

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.

Clinical experience with tamoxifen in peritoneal fibrosing syndromes.

Peritoneal sclerosis is one of the most important complications of peritoneal dialysis (PD) treatment. Encapsulating peritoneal sclerosis (EPS) represents the most advanced stage of that disease and has a high mortality. No therapy of choice has been established for sclerosing peritonitis, although many have been proposed, with variable results. Tamoxifen has been successfully used in the treatment of patients with fibrosing diseases, mainly retroperitoneal fibrosis. Our purpose in the present study was to investigate whether treatment with tamoxifen in PD patients with peritoneal sclerosis has a beneficial effect. Among more than 450 patients treated in our program since 1980, 23 were diagnosed with peritoneal sclerosis. Of those 23.9 were treated with tamoxifen [20 mg every 12 hours: tamoxifen group (TG)] for a mean period of 14.5 +/- 7 months (range: 6-30 months). The other 14 patients received no treatment and were considered the control group (CG). Both groups were similar in demography and peritoneal antecedents. Follow-up was longer in CG than in TG (mean: 47 months vs. 29 months), but the difference did not reach statistical significance. Mild thrombopenia in 1 patient was the only toxic effect observed with the use of tamoxifen. In CG, 4 patients developed EPS and died--3 of them during the first 6 months after diagnosis. No patient treated with tamoxifen developed EPS. Overall mortality was significantly higher in CG (71% vs. 22%, p = 0.03). Although follow-up was longer in CG, half the patients in that group died during the first 2 years after diagnosis. Our experience suggests that treatment with tamoxifen of patients diagnosed with peritoneal sclerosis diminishes the related complications and significantly reduces mortality, at least in the short- to mid-term. However, a prospective therapeutic trial is required to confirm our results.

Sequencing and G-quadruplex folding of the canine proto-oncogene KIT promoter region: might dog be used as a model for human disease?

Downregulation of gene expression by induction of non-canonical DNA structures at promotorial level is a novel attractive anticancer strategy. In human, two guanine-rich sequences (h_kit1 and h_kit2) were identified in the promotorial region of oncogene KIT. Their stabilization into G-quadruplex structures can find applications in the treatment of leukemias, mastocytosis, gastrointestinal stromal tumor, and lung carcinomas which are often associated to c-kit mis-regulation. Also the most common skin cancer in domestic dog, mast cell tumor, is linked to a mutation and/or to an over-expression of c-kit, thus supporting dog as an excellent animal model. In order to assess if the G-quadruplex mediated mechanism of regulation of c-kit expression is conserved among the two species, herein we cloned and sequenced the canine KIT promoter region and we compared it with the human one in terms of sequence and conformational equilibria in physiologically relevant conditions. Our results evidenced a general conserved promotorial sequence between the two species. As experimentally confirmed, this grants that the conformational features of the canine kit1 sequence are substantially shared with the human one. Conversely, two isoforms of the kit2 sequences were identified in the analyzed dog population. In comparison with the human counterpart, both of them showed an altered distribution among several folded conformations.

Peritoneal resting with heparinized lavage reverses peritoneal type I membrane failure. A comparative study of the resting effects on normal membranes.

BACKGROUND: Ultrafiltration failure (UFF) is a serious complication of long-term peritoneal dialysis (PD). Peritoneal rest (PR) has been demonstrated as a valid treatment to reverse the functional changes that occur in UFF. The effects of PR on a normally functioning human peritoneum are unknown but are expected to be neutral. Our hypothesis was that PR positively modifies peritoneal function in patients with UFF, in contrast to the absence of effects when PR is applied under normal conditions. PATIENTS AND METHODS: We studied 84 PR periods, comparing 35 patients with UFF and 49 controls (resting for abdominal surgery with temporary discontinuation of PD). We analyzed peritoneal transport pre-PR and post-PR by calculating the mass transfer coefficients of creatinine (Cr-MTAC), the dialysate/plasma creatinine ratio (D/P Cr) and the ultrafiltration (UF). RESULTS: Baseline data was similar for the 2 groups, although the UFF group had a longer median time in PD (39 [18 - 60] vs 10 [5 - 23] months; p = 0.00001). Peritoneal rest induced a decrease in D/P Cr, Cr-MTAC and an increase in UF capacity in the UFF group (p = 0.0001, p = 0.004 and p = 0.001, respectively), without causing changes in the control group. Peritoneal rest in patients with more than 6 months of UFF was not able to reduce peritoneal solute transport or improve UF capacity. Response to PR did not differ among UFF patients with or without a previous history of peritonitis. Peritoneal rest enabled patients with UFF to continue on PD for a median time of 23 months (range, 13 - 46 months). CONCLUSIONS: Peritoneal rest induces functional changes in patients with UFF but not in those with no functional abnormalities. This demonstrates that PR works only when abnormal but reversible functional conditions are present. However, the effect is highly dependent on how early PR is applied.

Pretransplant peritoneal dialysis relative to hemodialysis improves long-term survival of kidney transplant patients: a single-center observational study.

BACKGROUND: Kidney transplantation is the best option for the treatment of end-stage renal disease in terms of survival and quality of life. These results can be influenced by the pretransplant dialysis modality. The aim of this study was to evaluate whether the pretransplantation dialysis modality influences patient and allograft survival beyond 10 years and examine the potential risk factors associated with the outcomes. METHODS: We conducted an observational, retrospective, single-center clinical study that included 236 patients [118 undergoing peritoneal dialysis (PD) and 118 undergoing hemodialysis (HD)] who proceeded to transplantation during the period December 1990-2002. Donor and recipient data were collected from our hospital's clinical registries. The follow-up period extended to the patient's death, the loss of the allograft, or loss to follow-up. The end date of the study was set at March 2012. RESULTS: In the multivariate analysis, the long-term patient survival rate was higher for the PD group than for the HD group [HR = 2.62 (1.01-6.8); p = 0.04]; however, the allograft survival rate was not significantly different between the two groups [HR = 0.68 (0.41-1.10); p = 0.12]. CONCLUSION: Pretransplantation dialysis modality is associated with long-term patient survival, with outcomes favoring peritoneal dialysis over hemodialysis. However, the pretransplant dialysis modality does not influence long-term graft loss risk.