Correction: The modality of dialysis does not influence atheromatous vascular disease progression or cardiovascular outcomes in dialysis patients without previous cardiovascular disease.

[This corrects the article DOI: 10.1371/journal.pone.0186921.].

The modality of dialysis does not influence atheromatous vascular disease progression or cardiovascular outcomes in dialysis patients without previous cardiovascular disease.

BACKGROUND: There is limited and inconclusive information regarding the influence of the modality of renal replacement therapy on the atherosclerotic burden of patients on dialysis. The aim of this study was to compare the prevalence of asymptomatic atheromatous carotid disease, as also its rate of progression and cardiovascular outcomes, in two matched populations of patients treated with hemodialysis (HD) and peritoneal dialysis (PD). METHODS: Following a prospective, observational and multicenter design, we compared 237 PD and 237 HD patients without previous cardiovascular disease, included in the NEFRONA study, and matched for age, sex, diabetes and time on dialysis. Carotid ultrasound study was performed at baseline and after two years of follow-up in 6 carotid territories. Atheromatous vascular disease (AVD) progression was defined as any increase in the number of territories with plaques after 2 years. Fatal and non fatal cardiovascular events were also recorded during 36-month of follow-up. MAIN RESULTS: At baseline, PD patients presented a worse general cardiovascular risk profile than HD patients. On the contrary, some markers of prevalent atherosclerotic disease (common carotid intima-media thickness and ankle-brachial index) were more favorable in PD patients. During follow-up, we observed no differences either in the rate of progression of atheromatous vascular disease (OR 1.78, 95% CI 0.80-4.06, p = 0.161) or in the incidence of cardiovascular events (OR 1.51, 95% CI 0.85-2.66, p = 0.159), according to the modality of dialysis. CONCLUSION: Dialysis modality did not impact on atherosclerotic carotid disease progression or cardiovascular outcomes, in two groups of patients treated with PD or HD.

Effectiveness of treatment with oral paricalcitol in patients on peritoneal dialysis: a Spanish multicenter study.

AIMS: Recently, oral form of paricalcitol has allowed extension of treatment to ambulatory patients on peritoneal dialysis but few data have been published about the benefits of paricalcitol in this subgroup. A multicenter, retrospective study was carried out to increase current knowledge on the effectiveness and safety of paricalcitol in 162 peritoneal dialyzed patients with secondary hyperparathyroidism. METHODS: Case histories of patients treated with paricalcitol for at least 6 months were reviewed to extract data on 12 biochemical parameters related to bone disease and health status. Changes in these parameters were described. Doses of paricalcitol and other concomitant treatments were evaluated at least every 3 months. RESULTS: 99 men (61.1%) and 63 women (38.9%) with an average age of 62.07 years were included. PTH levels showed an acute decrease in the three first months (35.88%) and a global decrease at month 6 of 42.39%. A slight increase in calcium was observed (p < 0.001) but it remained between normal range values. Only 5 patients presented serum calcium over 10.2 in two consecutive measurements. No changes were found in phosphorus, calcium-phosphorus product, hemoglobin, alkaline phosphatase, GGT, albumin, PCR inflammatory markers, pH and bicarbonate. The decrease in proteinuria levels was nearly statistically significant (p = 0.061). Only 6 patients (0.36%) abandoned the treatment. CONCLUSIONS: Paricalcitol therapy was well tolerated with a high effectiveness in patients on peritoneal dialysis. A slight increase in serum calcium levels was observed, although within normal ranges. No changes in other biochemical parameters related to bone disease could be associated to paricalcitol with data compiled in our study. Paricalcitol seems to have a protective effect on proteinuria levels.

Goodpasture's syndrome associated with thrombotic thrombocytopenic purpura secondary to an ADAMTS-13 deficit.

A 27-year-old man was hospitalized for acute kidney injury associated with antiglomerular basement membrane antibodies (anti-GBM). He underwent immunosuppression and plasma exchange therapy, without recovery of renal function. Later on, he was again admitted to the hospital with seizures. Evidence of microangiopathic hemolytic anemia, with schistocytes in peripheral blood, was present, as well as a persistent low platelet count and activity of von Willebrand factor from adherence to protease (ADAMTS-13) less than 1 %. The presence of IgG antibodies against ADAMTS-13 was documented, leading to a diagnosis of thrombotic thrombocytopenic purpura (TTP) in the context of Goodpasture's syndrome. The TTP was treated with rituximab and plasmapheresis with a good response. We conclude that early measurement of ADAMTS-13 activity dictated the most appropriate therapy and achieved excellent results in this patient.

Higher daily peritoneal protein clearance when initiating peritoneal dialysis is independently associated with peripheral arterial disease (PAD): a possible new marker of systemic endothelial dysfunction?

BACKGROUND: Patients starting peritoneal dialysis (PD) with active cardiovascular disease (CVD) show higher protein and albumin levels in peritoneal effluent. Peripheral arterial disease (PAD) is increasingly recognized as an entity particularly associated with higher mortality. METHODS: To explore whether higher daily peritoneal protein clearance (PrC) on starting PD is a cardiovascular risk marker, we have formulated the hypothesis that PAD, as an expression of the highest CVD grade, is specifically related to the amount of PrC. RESULTS: The average of 24-h effluent peritoneal protein losses (PPL) was 6.88 +/- 3.31 g. The median of PrC was 94.43 ml/day and quartiles 1 and 4 were delimited by 56.25 and 114.18 ml/day, respectively. A significant positive correlation between PrC and peritoneal small solute transport was detected. Patients in the highest quintile of Cr-MTAC (>14.04 ml/min) demonstrated significantly greater PrC than the remainder. An inverse significant correlation with plasma albumin levels was also demonstrated (r = -0.52, P = 0.0001). Eighteen patients with PAD showed significantly higher PrC than patients with no PAD (130.62 +/- 74.89 versus 88.77 +/- 47.56 ml/day; P = 0.033). Other CVDs were not significantly associated with greater PrC. In the univariable logistic regression analysis, PAD was directly and significantly related to PrC, Charlson's index, gender, diabetes and age. Multivariable analysis confirmed that PAD was significantly related to PrC, independent of age (RR: 1.07, IC: 1.02-1.12, P = 0.006) and diabetes (RR: 11.29, IC: 2.9-42.60, P = 0.000). CONCLUSION: Our study shows that daily peritoneal PrC on initiating PD is significantly and independently related to the presence of PAD. Peritoneal PrC appears to be a possible new marker of systemic endothelial dysfunction.

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.

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.

Risk of technique failure and death in fungal peritonitis is determined mainly by duration on peritoneal dialysis: single-center experience of 24 years.

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.

Epithelial-to-mesenchymal transition of the mesothelial cell--its role in the response of the peritoneum to dialysis.

Peritoneal membrane fibrosis, ranging from mild inflammation to severe sclerosing peritonitis, is one of the complications of peritoneal dialysis (PD). In parallel with fibrosis, the peritoneum shows a progressive increase of capillaries and vasculopathy, involved in increased small solute transport across the membrane and ultrafiltration failure. Glucose and glucose degradation products from PD solutions are responsible of stimulating transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) production by mesothelial cells (MCs). TGF-beta is a potent pro-fibrotic factor and inducer of epithelial-to-mesenchymal transition (EMT) of the MC. Local production of VEGF by transitional MC appears to play a central role in the processes leading to peritoneal angiogenesis. This review addresses the mechanism involved in peritoneal structural alteration by dialysis and points to the EMT of MC as the initiating mechanism of peritoneal injury. Information from multiple origins about TGF-beta and VEGF is integrated into EMT process in a comprehensive manner. Regulation and new targets for inhibition of EMT or its deleterious effects are discussed.

The efficacy and safety of once-weekly and once-fortnightly subcutaneous epoetin beta in peritoneal dialysis patients with chronic renal anaemia.

BACKGROUND: Reducing the dosage frequency of subcutaneous epoetin in peritoneal dialysis (PD) patients is convenient and should improve patient satisfaction and, possibly, compliance. We investigated if a weekly dosage of epoetin beta in PD patients safely maintained haemoglobin (Hb) concentrations equivalent to those obtained with previous twice- or thrice-weekly administration. In addition, we investigated if a fortnightly dosage of epoetin beta was safe and as effective as previous weekly administration. METHODS: After a 4 week run-in period, PD patients were switched to either weekly or fortnightly epoetin beta administration, depending on their previous treatment schedules, for 25 weeks. RESULTS: The per-protocol cohort included 128 patients, of whom 54 received epoetin beta once weekly and 74 once fortnightly. The mean change in Hb concentration from baseline over weeks 13-25 and the 90% confidence intervals (CIs) remained within the target range (10-12 g/dl) and specified equivalence (+/-0.75 g/dl) limits in the weekly (-0.34 g/dl; 90% CI: -0.14 to -0.54 g/dl) and fortnightly (-0.39 g/dl; 90% CI: -0.24 to -0.55 g/dl) cohorts. The mean change from baseline in the epoetin beta dose was 1.4 IU/kg/week (90% CI: -3.8 to 6.6 IU/kg/week; 2%) in the weekly cohort and 4.4 IU/kg/week (90% CI: 1.7-7.2 IU/kg/week; 13%) in the fortnightly cohort. Both treatment regimens were well tolerated. CONCLUSIONS: In stable PD patients switched from twice- or thrice-weekly to weekly epoetin beta treatment, Hb concentrations could be maintained within the specified range over 25 weeks without significant change in their mean epoetin beta doses. In patients switched from weekly to fortnightly treatment, Hb concentrations could also be maintained over 25 weeks. There was a small increase in the mean dose during this period, but >/=50% of patients could be maintained without dose increase. Reducing dosage frequency may improve compliance in PD patients who self-administer their epoetin.

Low vs standard calcium dialysate in peritoneal dialysis: differences in treatment, biochemistry and bone histomorphometry. A randomized multicentre study.

BACKGROUND: In patients undergoing peritoneal dialysis (PD), low-calcium dialysate (LCD) has been proposed as the first choice for a better control of renal osteodystrophy. Our aim was to compare the effects on bone metabolism of LCD (calcium: 1.25 mmol/l) with that of a standard calcium dialysate (SCD; calcium: 1.75 mmol/l). METHODS: Forty-four PD patients were randomized to receive LCD or continue on SCD for a period of 12 months. Bone biopsies were taken at baseline and at 12 months. Biochemical data and treatment were evaluated every 3 months. RESULTS: Twenty-four patients completed the study. In the SCD group (n = 10), nine out of the 10 patients were initially diagnosed with adynamic bone lesion (ABL). After 1 year, six continued having ABL and three patients moved to high-turnover bone lesion (HTBL). The other patient, initially diagnosed with HTBL, changed to ABL. In the LCD group (n = 14), 10 patients were initially diagnosed with ABL. At 1 year, six of them continued having ABL and four patients changed to HTBL. Four patients were initially diagnosed with HTBL and did not change. Comparison between LCD and SCD groups showed an increase in serum parathyroid hormone (PTH) levels starting at month 3 and a higher intake of calcium salts in the former group (P<0.01). Serum calcium, phosphate levels and bone histological outcome did not differ between the two groups. CONCLUSIONS: LCD use for 1 year was associated with an increase in PTH levels, but did not lead to histological changes different from those observed in SCD group. The LCD solution allowed a higher oral intake of calcium salts with a satisfactory control of the serum Calcium-Phosphorus product.