Association between interleukin-10 gene polymorphism -592 (A/C) and peritoneal transport in patients undergoing peritoneal dialysis

Aim: The aim of this analysis was to know whether these three cytokine polymorphisms, including interleukin‐6 (IL‐6; ?572 G/C), tumour necrosis factor‐α (TNF‐α; ?308 G/A), and IL‐10 (–592 A/C) have an effect on baseline peritoneal transport property and longitudinal evolution of peritoneal function. Methods: A total of 141 stable peritoneal dialysis (PD) patients with mean treatment duration of 84.4 ± 34.2 months were enrolled. We genotyped these three cytokine polymorphisms, together with clinical parameters that were included as factors affecting longitudinal change of property of peritoneal transport over the first 3 year period after commencing therapy. Results: There was no significant association between genotypes and baseline peritoneal transport property. The ?592 A/C polymorphism of IL‐10 was associated with longitudinal change of peritoneal transport. The ratio of D/P creatinine was significantly higher in patients with AA than those with CC/CA genotypes at 12 months (0.65 ± 0.11 vs 0.62 ± 0.09, P = 0.048) and 24 months (0.64 ± 0.12 vs 0.59 ± 0.09, P = 0.018). In addition, patients with increased peritoneal transport have greater frequency distribution of AA genotype and A allele. Logistic regression analysis revealed that ?592 A allele was an independent predictor for the increase in D/P creatinine over the first 12 month period (odds ratio: 2.482, P = 0.017). There was no correlation between either polymorphism of IL‐6 ?572 (G/C) or TNF‐α?308 (G/A) and longitudinal change of peritoneal function. Conclusions: Single nucleotide polymorphism of IL‐10 ?592 (A/C) was associated with longitudinal evolution of peritoneal transport rate in PD patients rather than the baseline peritoneal characteristics.     

Conventional nutritional counselling maintains nutritional status of patients on continuous ambulatory peritoneal dialysis in spite of systemic inflammation and decrease of residual renal function

Aim: To evaluate the effect of nutritional counselling on nutritional status in peritoneal dialysis patients. Methods: Twenty‐nine peritoneal dialysis patients were randomly selected to receive conventional nutritional counselling during 6 months of follow up. All patients had monthly clinical and biochemical evaluations, and assessments of dialysis adequacy, inflammation and nutritional status at 0, 3 and 6 months. Results: Moderate‐severe malnutrition decreased 28% whereas normal nutrition increased 23% at final evaluation (non‐significant). Calorie and protein intake remained stable throughout the study (baseline vs final, calorie: 24 ± 8 vs 23 ± 5 Kcal/kg; protein: 1.1 ± 0.5 vs 1.0 ± 0.3 g/Kg, respectively). On the other hand, triceps (16 ± 6 vs 18 ± 8 mm) and subscapular (17 ± 8 vs 20 ± 5 mm) skinfold thicknesses, and mid‐arm circumference (27 ± 3 vs 28 ± 3 mm) significantly increased; mid‐arm muscle area displayed a non‐significant trend to increase (30 ± 9 vs 31 ± 9 cm²) whereas serum albumin significantly increased at the end of study (2.67 ± 0.46 vs 2.94 ± 0.48 g/dL). At final evaluation, median renal creatinine clearance decreased (6.3 (0.8–15.3) vs 2.0 (0.1–6.3) L/week per 1.73 m²) whereas interleukin‐6 increased (2.33 (1.9–7.0) vs 4.02 (2.1–8.4) pg/mL). Conclusion: Even though conventional nutritional counselling, as an isolated measure, did not significantly improve all nutritional parameters, it prevented a greater deterioration during 6 months. Nutritional counselling maintained the nutritional status in spite of a decrease in residual renal function and higher systemic inflammation.     

Comparison between standard single chamber versus dual chamber low glucose degradation product peritoneal dialysis fluids

Dual chamber (DC) peritoneal dialysis (PD) dialysates contain fewer glucose degradation products (GDPs), so potentially reducing advanced glycosylation end products (AGEs), which have been reported to increase inflammation and cardiovascular risk. We wished to determine whether use of DC dialysates resulted in demonstrable patient benefits. Biochemical profiles, body composition, muscle strength, and skin autofluorescence measurements of tissue AGEs (SAF) were compared in patients using DC and standard single chamber dialysates. We studied 263 prevalent PD patients from 2 units, 62.4% male, mean age 61.8 ± 16.1 years, 78 (29.7%) used DC dialysates. DC patients were younger (55.9 ± 16.4 vs. 64.2 ± 15.4 years), and more had lower Davies comorbidity score (median 1 (0‐1) vs. 1 (0, 2)), slower peritoneal transport (D/P creatinine 0.67 ± 0.12 vs. 0.73 ± 0.13), greater extracellular water‐to‐total body water (ECW/TBW) ratio (0.46 ± 0.05 vs. 0.42 ± 0.06), all P < .001, whereas there were no differences in the duration of PD (median (IQR) 19 (8‐32) vs. 14 (8‐23) months), residual renal function (Kt/V_urea 0.71 ± 0.71 vs. 0.87 ± 0.82), urine volume (642 (175‐1200) vs. 648 (300‐1200) mL/day), hand grip strength (26.9 ± 10.5 vs. 24.9 ± 10.7 kg), C‐reactive protein (4(1‐10) vs. 4(2‐12) mg/L), and SAF (median 3.60 (3.02, 4.40) vs. 3.50 (3.00, 4.23)) AU. In our cross‐sectional observational study, we were not able to show a demonstrable advantage for using low GDP dialysates over conventional glucose dialysates, in terms of biochemical profiles, residual renal function, muscle strength, or tissue AGE deposition. More patients using low GDP dialysates were slower peritoneal transporters with higher ECW/TBW ratios.     

The Effect of Colchicine on the Peritoneal Membrane

Peritoneal dialysis (PD) is a treatment modality for patients with renal failure. Peritoneal fibrosis is one of the most serious complications after long-term continuous ambulatory peritoneal dialysis (CAPD). Histological studies in both humans and animals show that chronic peritoneal dialysis results in fibrosis of the peritoneal membrane. In our study, we investigated the effect of colchicine on peritoneal alterations induced by hypertonic PD solution in rats. Sprague-Dawley rats intraperitoneally received saline (control group) once daily, for 28 days, or 3.86% glucose (PDF group), or 3.86% glucose plus colchicine (colchicine group). Animals from each group were sacrificed after 28 days with anesthetized ketamine (60 mg/kg BW). For the PD fluid assessment, 1 h before the sacrifice of animals, 10 mL PD fluid of 2.27% glucose was given, and this fluid was obtained after the sacrifice. The levels of transforming endothelial growth factor β (TGF-β), tumor necrosis factor α (TNF-α) and albumin were investigated both in the peritoneal dialysate and blood, and the levels of malondialdehyde (MDA) were investigated only in peritoneal dialysate. The peritoneal membrane was evaluated histologically by light microscopy. When groups were compared in terms of body weight change, the colchicine group significantly lost weight compared to controls and PDF group (?4.7% ± 4.5, 3.5% ± 7.2, 3.0% ± 1.3, respectively, p = 0.018). Also, the blood albumin level was significantly lower for these in the colchicine group compared to those in the PDF group (2.7 ± 0.35 versus 3.2 ± 0.3 g/dL, respectively, p = 0.048). The blood TGF-β level was significantly lower in the control group, and no difference was observed between the PDF and colchicine groups (294.4 ± 67.5 versus 787.4 ± 237.4 versus 615.3 ± 235.1 pg/mL, respectively, p = 0.004). The mesothelial thickness found in groups was as follows: control group 102 ± 18.9 µm, PDF group 128.33 ± 33.1 µm, colchicine group 117 ± 35.6 µm (p = 0.34). In conclusion, a rat model for peritoneal dialysis associated peritoneal derangement without fibrosis could be induced. Colchicine could not prevent peritoneal derangement in this model.     

Health-related quality of life,depression and mortality in peritoneal dialysis patients in Turkey: seven-year experience of a center

Introduction: Impairment of health-related quality of life (HRQoL) and being in a depressive mood were found to be associated with increased mortality in peritoneal dialysis (PD) patients. We aimed to investigate the association between HRQoL, depression, other factors and mortality in PD patients. Materials and methods: Totally 171 PD patients were included and followed for 7 years in this prospective study. Results: Of 171 PD patients, 45 (26.3%) deceased, 18 (10.5%) maintained on PD, 87 (50.9%) shifted to hemodialysis (HD) and 21 (12.3%) underwent transplantation. The most common cause of death was cardiovascular disease (32, 71.1%) followed by infection (6, 13.3%), cerebrovascular accident (5, 11.2%). The etiology of patients who shifted to HD was PD failure (41, 47.1%), peritonitis (33, 37.9%), leakage (6, 6.9%), catheter dysfunction (3, 3.4%), self willingness (4, 4.6%). Non-survivors were older than survivors (56.6?±?15.0 vs. 43.6?±?14.6, p?=?0.003). There were also statistically significant difference in terms of albumin, residual urine, presence of diabetes and co-morbidity. When the groups were compared regarding HRQoL scores, non-survivors had lower physical functioning (p?<?0.001), role-physical (p?=?0.0045), general health (p?=?0.004), role-emotional (p?=?0.011), physical component scale (PCS) (p?=?0.004), mental component scale (MCS) (p?=?0.029). Age, presence of residual urine, diabetes, albumin, PCS and MCS were entered in regression analysis. Decrease of 1?g/dL of albumin and being diabetic were found to be the independent predictors of mortality. Conclusions: Diabetes and hypoalbuminemia but not HRQOL scores were associated with higher mortality in PD patients after 7 years of following period.     

Effect of renin–angiotensin system inhibitors on prevention of peritoneal fibrosis in peritoneal dialysis patients

Aim: Long‐term peritoneal dialysis (PD) may lead to peritoneal fibrosis and ultrafiltration failure. It had been demonstrated that the renin–angiotensin system (RAS) plays a key role in the regulation of peritoneal function in rats on PD. We investigated the effects of angiotensin‐converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) on long‐term PD patients. Methods: We analyzed data from 66 patients treated with PD therapy at our centre for at least 12 months retrospectively, during which time at least two peritoneal equilibration tests (PET) were performed. Thirty‐eight patients were treated with ACE/angiotensin II (AII) inhibitors (ACE/ARB group); the other 28 received none of the above drugs during the entire follow up (control group). The expression of fibronectin, transforming growth factor‐β1 (TGF‐β1), Aquaporin1 (AQP1) and vascular endothelial growth factor (VEGF) in the overnight effluent were examined by enzyme‐linked immunosorbent assay. Results: The demographic data of the two groups showed no difference during the study. No difference between the groups was found with respect to residual renal function (RRF) at the start for both groups by the end of follow up, decreased in the vast majority of patients from both groups (P = 0.014). After 12 months, a significant difference in ultrafiltration was found between the two groups: in the control group it had decreased, while it had not changed in the ACE/ARB group (P < 0.05). In comparison with the baseline level, expression of fibronectin, TGF‐β1 and VEGF in dialysate effluent were significantly increased except for AQP1 in the control group (P < 0.05), but not in the ACE/ARB group (P > 0.05). Conclusion: The findings suggest that ACE/AII inhibitors appeared to have a slower rate of decline in ultrafiltration and RRF, effectively protect against peritoneal fibrosis in long‐term peritoneal dialysis. Long‐term follow up seems to be required to draw more conclusions.     

A high peritoneal large pore fluid flux causes hypoalbuminaemia and is a risk factor for death in peritoneal dialysis patients.

BACKGROUND: Hypoalbuminaemia is common in peritoneal dialysis (PD) patients and has an associated high mortality. An excess morbidity and mortality has previously been found in patients with high peritoneal transport. A high peritoneal large pore fluid flux (Jv(L)) results in increased peritoneal loss of protein that possibly contributes to patient morbidity. Alternatively, hypoalbuminaemia and high transport status could be just a marker of capillary pathology associated with atherosclerotic comorbidity. METHODS: Peritoneal dialysis capacity computer modelling of peritoneal transport, based on Rippe's three-pore model, was performed to measure Jv(L) in 155 incident PD patients 2-4 weeks after PD initiation. Patient clinical and biochemical status was determined -6, -3, -1, 1 and 6 months after PD initiation, and every 6 months thereafter. Jv(L) was redetermined in prevalent patients 2 and 4 years after PD initiation. RESULTS: Jv(L) was 0.106+/-0.056 ml/min/1.73 m(2) (median 0.094, interquartile range 0.068-0.128). It was correlated to age*** (*P<0.05; **P<0.01; ***P<0.001) (20-30 years 0.079+/-0.04; 70 years 0.121+/-0.071), but not to gender. No correlation to diabetic or preexisting renal replacement therapy was seen, but patients with atherosclerosis had higher Jv(L) (0.123+/-0.06 vs 0.100+/-0.056*) as had patients with other systemic disease (0.121+/-0.68 vs 0.100+/-0.051*). Jv(L) was positively correlated to area parameter (r = 0.41***), and negatively correlated to plasma albumin (-0.36***). Patients were divided into three equal groups: group 1, Jv(L) <0.075 ml/min/1.73 m(2); group 2, 0.075-0.11; group 3: >0.11. There was no difference between the groups in p-albumin prior to PD. Immediately after PD start, differences between the three groups appeared (1 month p-albumin: (micromol/l) group 1, 548+/-83; group 2, 533+/-86; group 3, 497+/-78**), and persisted for up to 6 years. No significant change in Jv(L) was seen at 2 and 4 years. Patients with significant albuminuria also had hypoalbuminaemia (<1 g/day: 546+/-81 mumol/l; >2 g/day: 503+/-54 micromol/l). Intermittent PD ameliorated the effect of Jv(L) on albumin losses and clearance. Mortality was increased significantly with raised Jv(L), independently of age (2 year mortality: group 1, 10%, group 3, 32%*). There was no overall effect on technique survival, but hypoalbuminaemic group 3 patients had a higher failure rate. CONCLUSION: Jv(L) is related to hypoalbuminaemia and mortality after PD initiation. A high Jv(L) seems to be a marker of preexisting vascular pathology, and to cause hypoalbuminaemia after PD initiation. It is suggested that peritoneal albumin loss can have an identical pathogenic effect as urinary albumin loss, by causing an iatrogenic "nephrotic" syndrome.     

Intraperitoneal heparin reduces peritoneal permeability and increases ultrafiltration in peritoneal dialysis patients.

BACKGROUND: Patients on long-term treatment with peritoneal dialysis (PD) suffer from increasing peritoneal permeability and loss of ultrafiltration as a result of persistent inflammation, which may be triggered by bioincompatible dialysis fluids. Heparins have anti-inflammatory and anticoagulant properties. We have examined the effect of intraperitoneal (IP) low-molecular weight heparin (tinzaparin) on peritoneal permeability and ultrafiltration in PD patients. METHODS: By means of a double-blinded cross-over design, 21 PD patients were randomized to receive either placebo or tinzaparin intraperitoneally once a day for two treatment periods of 3 months, separated by a wash-out period. The effect of heparin on peritoneal permeability and ultrafiltration was assessed using the 4 h standard peritoneal equilibration test. RESULTS: IP tinzaparin reduced significantly the dialysate-to-plasma ratios (D/P) of creatinine (P < 0.01), urea (P < 0.01) and albumin (P<0.05). In addition, the ratio of glucose concentration in dialysate at 4 h dwell to that of 0 h dwell (D(4)/D(0)) was increased (P<0.05) along with an increase in ultrafiltration volume (P<0.05). CONCLUSIONS: IP tinzaparin reduces peritoneal permeability to small solutes and increases ultrafiltration in PD patients.     

The effectiveness of oral essential aminoacids and aminoacids containing dialysate in peritoneal dialysis

Background/Aim: Oral essential amino acids (AAs) containing supplements (EAS) and AA containing dialysate (ACD) are frequently used in peritoneal dialysis (PD) patients with malnutrition. The present study was conducted to investigate two strategies and compare their effects on the malnutrition status of PD patients. Materials and Methods: A total of 31 EAS, 14 ACD patients were enrolled in this study. Serum albumin levels were lower than 3.5?g/dL in all subjects. EAS group patients took five pills containing AAs three times a day with meals. In the other, 2.000?cc of 1.1% ACD was given to patients daily during the study. Demographic and laboratory parameters were analyzed and compared at baseline and 6th month. Results: Significant increases in BMI, albumin, and protein in both groups. Mean albumin levels increased significantly by 0.54?g/dL in ACD group (p?0.005) and 0.49?g/dL in EAS group (p?0.001) following 6 months. Mean albumin and delta albumin levels did not differ between two groups. Conclusion: These strategies may play an important role in increasing albumin levels and improving the nutritional status of PD patients.     

Relation of ankle-brachial index to the rate of decline of residual renal function in peritoneal dialysis patients

Aim: The aim of this study was to determine whether ankle‐brachial index (ABI) predicts the rate of decline of residual renal function (RRF) in peritoneal dialysis (PD) patients. Previous studies demonstrated the importance of loss of RRF in predicting all‐cause risk and cardiovascular mortality in PD patients. It is also known that patients with a low ABI value have a greater risk for deteriorating renal function in the general population. The relationship between ABI and the declining rate of RRF in PD patients with an additional dialysis‐specific risk factor is uncertain. Methods: Seventy‐four PD patients with RRF of more than 1 mL/min per 1.73 m² were analyzed. ABI was used as the surrogate measure of pre‐existing cardiovascular disease and atherosclerosis burden to further determine the outcome of RRF in this study. The slope of decline of RRF was used to determine the outcome. Results: Based on the multivariate analysis, only ABI (P < 0.001), diabetes (P = 0.02) and baseline RRF (P = 0.009) independently predicted a faster decline in RRF. A stepwise multiple linear regression analysis demonstrated that ABI was an independent predictor for the slope of decline of RRF (P < 0.001). Conclusion: A low ABI is an independent predictor of not only the known atherosclerotic events, but also of the rate of decline of RRF over time in PD patients.     

Elevated Plasma Levels of PAI-1 Predict Cardiovascular Events and Cardiovascular Mortality in Prevalent Peritoneal Dialysis Patients

Background. Elevated plasminogen activator inhibitor-1 (PAI-1) levels are associated with increased cardiovascular (CV) risk in the general population. It has been shown that peritoneal dialysis (PD) patients have increased plasma levels of PAI-1. The aim of this study was to investigate whether PAI-1 independently predicted CV outcome in PD patients. Material and Methods. Seventy-two PD patients (53% females, mean age 49.9 ± 16.1 years) were studied. Twelve patients who underwent kidney transplantation and 14 patients who transferred to hemodialysis during follow-up were excluded from the analysis. The remaining 46 patients (54% female, mean age 54 ± 16 years, dialytic age 42 ± 30 months) were followed a mean time of 45.4 ± 19.4 months (range 8–71 months). Baseline PAI-1, clinical, and laboratory parameters were assessed in all patients. Survival analyses were made with Kaplan-Meier and Cox regression analysis, with all-cause mortality and CV mortality and CV events (CVEs) as clinical end points. Results. During the follow-up, 29 patients died (17 from CV causes), and 28 fatal and non-fatal CVEs were recorded. The patients were divided according to plasma PAI-1 levels (i.e., ≤ or >41 ng/mL). The significant independent predictors of all-cause of mortality were age (60 years; p = 0.018), CRP (5 mg/L; p = 0.015), and serum albumin (<3.5 g/L; p = 0.011). Multivariable Cox regression analysis showed that plasma PAI-1 41 ng/mL was independently predictive of higher CV mortality (p = 0.021) and CVEs (p = 0.001). The only other independent predictor of CV mortality was only CRP (5 mg/L; p = 0.008). Conclusions. Plasma levels of PAI-1 41 ng/mL is a significant predictor of CV mortality and CVEs in PD patients.     

Twenty four‐hour ambulatory blood pressure profiles 12 months post living kidney donation

Small blood pressure (BP) elevations may occur post kidney donation. This prospective study determined 24‐h ambulatory BP (ABP) and other cardiovascular risk factor changes in 51 living donors over 12 months postdonation. Donors also provided 24‐h urine collections for monitoring protein and creatinine clearance, 75 g oral glucose tolerance tests (OGTT), and fasting lipids. Nondipping was defined as night‐day systolic (SBP) ratio ≥0.9. Baseline and 12‐month pre to postdonation comparisons were made both for dippers and nondippers. Of 51 donors, 35 were dippers and 16 nondippers. In these two groups, predonation 24‐h SBP were 115.2 ± 8 and 115.6 ± 10 mmHg; serum creatinine (SCr) 69.3 ± 12 and 71.1 ± 13 μmol/l; and 24‐h urine protein 0.12 ± 0.05 and 0.09 ± 0.03 g (all P = NS) while at 12 months, 24‐h SBP were 111.4 ± 11 and 114.3 ± 8 mmHg (P = 0.384), SCr 97.9 ± 16 and 97.7 ± 21 μmol/l (P = 0.810); and 24‐h urine protein 0.139 ± 0.09 and 0.111 ± 0.07 g/d (P = 0.360) respectively. The 24‐h SBP was significantly lower in the dippers at 12 months as compared with predonation (P = 0.036). OGTT and lipid profiles remained normal in both groups. Predonation nocturnal nondipping does not carry adverse postdonation consequences over 12 months.     

Bidirectional peritoneal transport of albumin in continuous ambulatory peritoneal dialysis

The present study was undertaken in order to assess bidirectionalperitoneal kinetics of albumin after simultaneous i.v. and i.p.injection of radioiodinated albumin tracers (¹²⁵I-RISA and ¹³¹I-RISA)in eight clinically stable uraemic patients undergoing continuousambulatory peritoneal dialysis (CAPD). The plasma volume, intravascularalbumin mass (IVM), and overall extravasation rate of albuminwere not significantly different from that found in healthycontrols. Albumin flux from the plasma into the peritoneal cavitywas 3.71 ± 0.82 (SD) µmol/h, which was only 3%of the overall extravasation rate (137 ± 52 µmol/h).Albumin flux from the peritoneal cavity into the plasma wassubstantially lower (0.22 ± 0.07 µmol/h, P<0.01).The net peritoneal accumulation of the albumin from plasma over4 h was 14 ± 3.2 µmol, which was significantlylower than the intraperitoneal albumin mass at the end of thedialysis (54 ± 19 µmol, P<0.01). This indicatesthat only about 25% of the albumin loss during CAPD occurs directlyfrom the plasma. The initial osmotic net filtration was 508± 302 ml. The volume flow equivalent to the albumin fluxwas 6.3 ± 1.5ml/h into the peritoneal cavity and 7.8± 1.9ml/h back into the plasma. Although minor, as comparedto the osmotic net filtration (508 ml), the albumin flux equivalentvolume (31.2 ml) exceeded the steady state filtration (25.2ml) significantly (P<0.01) during the 4 h investigation. In conclusion, albumin flux into the peritoneal cavity is smallcompared to the overall extravasation rate, but our resultssuggest that CAPD loss of albumin predominantly occurs fromthe subperitoneal interstitial space and only to a minor degreedirectly from the plasma. Albumin flux equivalent volume flowis relatively small and most probably represents peritoneallymph drainage.     

High mobility group box 1 and tumor growth factor β: useful biomarkers in pediatric patients receiving peritoneal dialysis

Background: Peritonitis, the most important limitation of peritoneal dialysis (PD), could be detected by biomarkers in dialysate effluent, representing a noninvasive method to indirectly assess the peritoneum status. The aim of our study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating its role as precocious marker of peritoneum damage during peritonitis. Transforming growth factor (TGF)-β was correlated with peritoneal transport characteristics.

Methods: Six patients, treated by ambulatory PD, were enrolled. Samples were collected at the onset of peritonitis (T1) and every day until its resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was also evaluated. Peritoneal Equilibration Test evaluated the filter activity of peritoneum.

Results: In patients with acute peritonitis, the highest serum and peritoneal HMGB1 values (64?±?3.6 and 70?±?5.3?ng/mL, respectively) were assessed, with a progressive decrease of their levels at the resolution time (T-end: sHMGB1:36?±?2.5; pHMGB1:30.5?±?7.0?ng/mL). While no differences of sWBC and pWBC were observed between baseline and T-end values, pHMGB1 levels remained higher at T-end than those observed at T0 (pHMGB1:30.5?±?7.0 versus 6.9?±?3.6; p?p?=?0.01). An inverse correlation was found between TGF-β levels and dialysate/plasmatic creatinine values (r = ?0.83; p?=?0.03).

Conclusion: HMGB1 represents a useful biomarker for peritoneum evaluation in PD patients. A prognostic role of this alarmin, as a marker of response to therapy, could be hypothesized. TGF-β could predict the peritoneal transport status and dialysis technique adequacy.     

The importance of ultrasonographic measurement of peritoneal wall thickness in pediatric chronic peritoneal dialysis patients

Abstract

Loss of peritoneal function due to peritoneal fibrosing syndrome (PFS) is a major factor leading to treatment failure in chronic peritoneal dialysis (PD) patients. Although the precise biologic mechanisms responsible for these changes have not been defined, the general assumption is that alterations in peritoneal function are related to structural changes in the peritoneal membrane. Studies of the peritoneal membrane by non-invasive ultrasonography (US) in chronic PD patients are limited. The aim of the present study is to assess the relationship between functional parameters of peritoneum and peritoneal thickness measured by US in children treated by chronic PD. We recruited two groups of patients: 23 subjects (13 females, 10 males) on chronic PD (patient group) and 26 (7 females, 19 males) on predialysis out-patient follow-up (creatinine clearance: 20–60?mL/min/1.73?m²) (control group). Age, sex, weight, height, body mass index (BMI), chronic PD duration, episodes of peritonitis and the results of peritoneal equilibration test (PET) were recorded. Hemoglobin (Hb), blood pressure (BP), left ventricular mass index (LVMI) and renal osteodystrophy (ROD) parameters were also obtained. The thickness of the parietal peritoneum was measured by trans-abdominal US in all children. Statistical analyses were performed by using Student's t and Pearson's correlation tests. Mean peritoneal thickness in chronic PD patients (1028.26?±?157.26?μm) was significantly higher than control patients (786.52?±?132.33). Mean peritoneal thickness was significantly correlated with mean body height (R²?=?0.93, p?<?0.05), BMI (R²?=?0.25, p?<?0.05), chronic PD duration (R²?=?0.64, p?<?0.05), episodes of peritonitis (R²?=?0.93, p?<?0.05), D/P_creatinine (R²?=?0.76, p?<?0.05) and D4/D0_glucose (R²?=?0.81, p?<?0.05). No correlation was found between peritoneal thickness and Hb, BP, LVMI and ROD parameters. In conclusion, ultrasonographic measurement of peritoneal membrane thickness is a simple and non-invasive method in chronic PD children. This diagnostic tool likely enables to assess peritoneal structure and function in these patients.     

Treatment with a cyclin-dependent kinase inhibitor, seliciclib, is effective in reducing glomerular macrophage numbers and the severity of established experimental glomerulonephritis

Aim: The cyclin‐dependent kinase inhibitor, seliciclib (R‐roscovitine, CYC202), has anti‐proliferative activity through its inhibition of cyclin‐dependent kinase 2. We hypothesized that treatment with seliciclib would reduce glomerular macrophage numbers and glomerular crescent formation in experimental crescentic glomerulonephritis even when treatment is started after onset of disease. Method: Nephrotoxic nephritis (NTN) was induced in Wistar Kyoto rats. In experiment 1, seliciclib (150 mg/kg per day) was given by oral gavage from 1 h before induction of NTN and continued to day 14. In experiment 2, treatment was started on day 4 of NTN and continued to day 14 in order to examine the effect of seliciclib in established glomerulonephritis. Results: In experiment 1, seliciclib reduced proteinuria (119.5 ± 13.9 vs 191.4 ± 18.8 mg/day, P < 0.01), serum creatinine (54.0 ± 3.0 vs 81.0 ± 2.5 µmol/L, P < 0.005) and glomerular crescent score (23.9 ± 2.1 vs 44.6 ± 2.2, P < 0.005) in comparison with controls. In experiment 2, seliciclib ameliorated established glomerulonephritis, with reduction in proteinuria (58 ± 16 vs 165 ± 13 mg/day, P < 0.005), serum creatinine (39 ± 3 vs 62 ± 5 µmol/L, P < 0.05), glomerular macrophage numbers (6.8 ± 2.5 vs 18.5 ± 1.2 ED1+ cells per glomerular cross section, P < 0.05), glomerular cell proliferation (1.2 ± 0.37 vs 4.2 ± 0.80 bromodeoxyuridine (BrdU)+ cells per glomerular section, P < 0.05) and crescent score (10.8 ± 1.6 vs 43.9 ± 1.4, P < 0.05), in comparison with the controls. Conclusion: Seliciclib is effective in both prevention and treatment of established crescentic glomerulonephritis in Wistar Kyoto rats, in association with a reduction in the number of glomerular macrophages. We suggest that seliciclib, or other cyclin‐dependent kinase inhibitors, may represent a novel therapeutic approach for patients with proliferative glomerulonephritis.     

The impact of diabetes mellitus on peritoneal dialysis: the Turkey Multicenter Clinic Study

Purpose: It is well established that diabetic peritoneal dialysis (PD) patients have a higher mortality rate than the other PD population. This study was designed to determine the overall predictors of survival and compared mortality and morbidity between diabetic and non-diabetic Turkish PD patients. Methods: We conducted a multicenter retrospective study with 915 PD patients [217 had diabetes mellitus (DM)]. Serum albumin, PTH, HbA1c, co-morbid diseases, dialysis adequacy (Kt/V), and peritoneal transport characteristics as well as peritonitis episodes and ultrafiltration failure during the follow-up period were recorded. Results: DM patients were older and had more co-morbidities than non-DM patients. Peritonitis rates were higher in DM patients (one episode per 35.9 patient months) compared to non-DM patients (one episode per 41.5 patient months) (p?p?=?0.022), age (HR 1.03, p?p?p?=?0.038), peripheral artery disease (HR 1.83, p?=?0.025) and amputation (HR 4.1, p?=?0.009) at baseline were significant predictors of overall mortality. Conclusions: Patient survival is lower in diabetic compared to non-diabetic patients on PD. Peritonitis rates were also higher in diabetic PD patients. DM, older age, albumin level and cardiovascular co-morbidities are predictors of mortality     

Randomized trial comparing pulse calcitriol and alfacalcidol for the treatment of secondary hyperparathyroidism in haemodialysis patients

Aim: Calcitriol and alfacalcidol are used extensively for the treatment of secondary hyperparathyroidism. Unfortunately, there is limited published data comparing the efficacy and tolerability of both active vitamin D sterols. This study was undertaken to determine whether calcitriol provides a therapeutic advantage to alfacalcidol. Methods: This was a randomized, active controlled study. Patients with intact parathyroid hormone (iPTH) >32 pmol/L were randomized to receive orally calcitriol or alfacalcidol after each haemodialysis for up to 24 weeks. Reduction of PTH, changes of plasma albumin‐corrected calcium and phosphorus were analysed. The initial dose of alfacalcidol was twice that of calcitriol. Results: Sixteen patients were randomized into each group. At baseline, plasma albumin‐corrected calcium, phosphorus and PTH were no different between groups. At 24 weeks, PTH changes were ?50.8 ± 31.8% and ?49.4 ± 32.5% from the baseline in the calcitriol and alfacalcidol groups, respectively (P = 0.91). The patients who achieved target PTH of 16–32 pmol/L were 82% in the calcitriol and 67% in the alfacalcidol group (P = 0.44). Plasma albumin‐corrected calcium and phosphorus were not significantly different but showed trends toward gradually increasing from baseline in both groups (calcium, 6.0 ± 7.2% vs 10.9 ± 6.5% (P = 0.10); phosphorus, 13.0 ± 29.4% vs 16.7 ± 57.2% (P = 0.83) in calcitriol and alfacalcidol, respectively). The mean dose of calcitriol and alfacalcidol were 4.1 and 6.9 µg/week, respectively (P < 0.0001). Conclusion: Alfacalcidol can be used to control secondary hyperparathyroidism at doses of 1.5–2.0 times that of calcitriol. The two drugs are equally efficacious and lead to similar changes in calcium and phosphorus.