Aiwu Lin

Better preservation of residual renal function in peritoneal dialysis patients treated with a low-protein diet supplemented with keto acids: a prospective, randomized trial

BACKGROUND While a low-protein diet may preserve residual renal function (RRF) in chronic kidney disease (CKD) patients before the start of dialysis, a high-protein intake is usually recommended in dialysis patients to prevent protein-energy wasting. Keto acids, which were often recommended to pre-dialysis CKD patients treated with a low-protein diet, had also been reported to be associated with both RRF and nutrition maintenance. We conducted a randomized trial to test whether a low-protein diet with or without keto acids would be safe and associated with a preserved RRF during peritoneal dialysis (PD). METHODS To assess the safety of low protein, we first conducted a nitrogen balance study in 34 incident PD patients randomized to receive in-centre diets containing 1.2, 0.9 or 0.6 g of protein/kg ideal body weight (IBW)/day for 10 days. Second, 60 stable PD patients [RRF 4.04 +/- 2.30 ml/ min/1.73 m(2), urine output 1226 +/- 449 ml/day, aged 53.6 +/- 12.8 years, PD duration 8.8 (1.5-17.8) months] were randomized to receive either a low- (LP: 0.6-0.8 g/kg IBW/day), keto acid-supplemented low- (sLP: 0.6-0.8 g/kg IBW/day with 0.12 g/kg IBW/day of keto acids) or high-protein (HP: 1.0-1.2 g/kg IBW/day) diet. The groups were followed for 1 year and RRF as well as nutritional status was evaluated serially. RESULTS A neutral or positive nitrogen balance was achieved in all three groups. RRF remained stable in group sLP (3.84 +/- 2.17 to 3.39 +/- 3.23 ml/min/1.73 m(2), P = ns) while it decreased in group LP (4.02 +/- 2.49 to 2.29 +/- 1.72 ml/min/1.73 m(2), P < 0.05) and HP (4.25 +/- 2.34 to 2.55 +/- 2.29 ml/min/1.73 m(2), P < 0.05). There was no change from baseline on nutritional status in any of the groups during follow-up. CONCLUSIONS A diet containing 0.6-0.8 g of protein/kg IBW/day is safe and, when combined with keto acids, is associated with an improved preservation of RRF in relatively new PD patients without significant malnutrition or inflammation.

Comparison of peritoneal dialysis practice patterns and outcomes between a Canadian and a Chinese centre

UNLABELLED Objective. We compared patient characteristics, dialysis practice patterns and outcomes of peritoneal dialysis (PD) patients between one Chinese centre and one Canadian centre to determine whether observed differences in demographics and practices are associated with patient and technique survival. METHODS This study included all patients who started on PD between 1 January 2000 and 31 December 2004 at the University Health Network, University of Toronto, Canada and Renji Hospital, Shanghai Jiao Tong University School of Medicine, China. They were followed up from the date of PD initiation until death, cessation of PD, transfer to other centres or to the end of the study (31 December 2006). RESULTS We studied 496 patients, 256 from the Canadian centre and 240 from the Chinese centre. Canadian patients were older and more likely to have diabetes and cardiovascular comorbidities at the initiation of PD, while the Chinese patients had lower residual renal function (RRF). More Canadian patients were treated with APD, whereas all Chinese patients were on CAPD with a lower PD volume. Crude patient survival rates at 1, 2, 3 and 5 years were similar between the two centres: 90%, 79%, 72% and 61% for Canadian and 90%, 79%, 71% and 64% for Chinese patients, respectively. After adjustment for demographic and clinical variables, there is no significant difference in mortality between Chinese patients and Canadian patients. Age, cardiovascular disease, diabetes, RRF and serum albumin were independent predictors of patient survival. The death-censored technique survival rates were significantly lower among the Canadian patients compared to Chinese patients. Chinese patients showed a lower risk of technique failure (HR 0.491, 95% CI 0.269-0.898, P = 0.021) after adjustment for patient characteristics. Chinese centre, BMI, serum albumin and gender were independent predictors of technique survival. The average peritonitis rate was one episode every 36.1 patient-months in Canadian patients and one episode every 60.6 patient-months in their Chinese counterparts. CONCLUSION Patient characteristics, dialysis practice patterns and outcomes vary between Canadian and Chinese patients. The variability in patient outcomes between these two centres indicates that further improvements may be possible in both centres. We have identified several areas for improving outcomes.

Daily peritoneal ultrafiltration predicts patient and technique survival in anuric peritoneal dialysis patients

BACKGROUND Maintenance dialysis therapy is the only way to remove excess fluid in patients with anuric end-stage renal disease. The optimal ultrafiltration (UF) volume in patients on peritoneal dialysis (PD) remains controversial. METHODS We retrospectively analysed a cohort of 86 prevalent anuric PD patients followed up for a median of 25.3 months (range, 6 to 54 months). Clinical and PD parameters were recorded yearly. Kaplan-Meier analysis and Cox proportional hazards models were used to identify risk factors of mortality and technique failure in patients with a UF >/=1 L/24 h or <1 L/24 h. RESULTS When compared to those with a UF <1 L/24 h, patients with a UF >/=1 L/24 h had significantly higher haemoglobin levels (101.9 +/- 20.5 vs 89.3 +/- 20.2 g/L, P < 0.05) and tended to be younger (55.0 +/- 12.5 vs 60.6 +/- 16.1 years, P = 0.10). Also, while Kt/V and CCr were stable over time, UF decreased significantly over the study period (baseline, 1205.5 +/- 327.3 ml/24 h vs after 3 years, 870.6 +/- 439.8 ml/24 h; P < 0.001). Using Kaplan-Meier analysis, patients with baseline UF <1 L/24 h had significantly worse outcome (survival, 27.2 +/- 3.9 vs 42.4 +/- 1.9 months; P < 0.001). In multivariate Cox regression analysis, age, time-dependent UF volume and serum albumin were independent predictors of mortality, while UF independently predicted technique failure. CONCLUSIONS The present study demonstrates a strong predictive value of daily peritoneal UF for both technique and patient survival in prevalent anuric PD patients. Identifying markers of satisfactory fluid status, as well as optimizing therapy to meet UF goals, remains an important clinical target.

Adiponectin Is Related to Carotid Artery Plaque and a Predictor of Cardiovascular Outcome in a Cohort of Non-Diabetic Peritoneal Dialysis Patients

Aims: Adiponectin is an adipocytokine with antiatherogenic and anti-inflammatory properties. We investigated associations between circulating adiponectin, inflammation and cardiovascular disease in peritoneal dialysis patients. Methods: A prospective study was performed in 59 non-diabetic patients. The concentrations of serum adiponectin, biochemical data and ultrasound of carotid artery were measured at enrollment. The patients were followed up to 39 months mainly for cardiovascular events. Results: The serum adiponectin concentration was elevated and inversely related to C-reactive protein and interleukin-6 in the patients. The adiponectin level of patients with carotid plaques was significantly lower than in those without plaques (p < 0.01). Kaplan-Meier analysis showed that the cumulative survival without new cardiovascular events was better in patients with higher adiponectin levels than in those with lower adiponectin levels. Conclusion: Serum adiponectin levels are inversely related with markers of systemic inflammation and signs of atherosclerosis which may explain why hyperadiponectinemia in this study was associated with better cardiovascular outcome.

Design and challenges of the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (RENAL) Trial: high-dose versus standard-dose hemofiltration in acute renal failure

Background/Aims: The optimal dose of renal replacement therapy (RRT) in acute renal failure (ARF) is uncertain. Methods: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy Trial tests the hypothesis that higher dose continuous veno-venous hemodiafiltration (CVVHDF) at an effluent rate of 40 ml/kg/h will increase survival compared to CVVHDF at 25 ml/kg/h of effluent dose. Results: This trial is currently randomizing critically ill patients in 35 intensive care units in Australia and New Zealand with a planned sample size of 1,500 patients. This trial will be the largest trial ever conducted on acute blood purification in critically ill patients. Conclusion: A trial of this magnitude and with demanding technical requirements poses design difficulties and challenges in the logistics, conduct, data collection, data analysis and monitoring. Our report will assist in the development of future trials of blood purification in intensive care. This study was registered with ClinicalTrials.gov (NCT00221013).

Impact of Break-In Period on the Short-Term Outcomes of Patients Started on Peritoneal Dialysis

♦ Objectives: Peritoneal dialysis (PD) is one of the first-line modalities of renal replacement therapy in patients with end-stage renal disease. Guidelines recommended a break-in period of at least 2 weeks before full PD start. However, the optimal duration of the break-in period is still unclear. In the present study, we investigated the effect of various break-in periods on short-term outcomes in patients on PD. ♦ Methods: All patients who underwent Tenckhoff catheter implantation and initiated PD in Renji Hospital, Shanghai Jiao Tong University School of Medicine, between 1 January 2001 and 31 December 2010 were included. Patients were grouped according to the duration of their break-in period: 7 days or less (BI≤7), 8 - 14 days (BI8-14), and more than 14 days (BI>14). Kaplan-Meier curves and log-rank tests were used to compare short-term outcomes in the various groups. ♦ Results: Our study enrolled 657 patients (44.5% men), of whom 344, 137, and 176 patients were in the respective break-in groups. Compared with BI>14 patients, BI≤7 patients had a lower estimated glomerular filtration rate (5.34 ± 1.86 mL/min/1.73 m2 vs 6.55 ± 1.71 mL/min/1.73 m2, p < 0.001) and lower serum albumin (33.29 ± 5.36 g/L vs 36.64 ± 5.40 g/L, p < 0.001). The incidence of mechanical complications during the first 6 months was significantly higher in BI≤7 patients than in BI>14 patients (8.4% vs 1.7%, p = 0.004). However, we observed no significant differences between the three groups with respect to the prevalence of catheter dysfunction requiring surgical intervention (p > 0.05). Logistic regression analysis showed that BI≤7 [relative risk: 4.322; 95% confidence interval (CI): 1.278 to 14.608; p = 0.019] was an independent predictor of catheter dysfunction, but not of catheter dysfunction requiring surgical intervention (p > 0.05). Catheter dysfunction [hazard ratio (HR): 20.087; 95% CI: 7.326 to 55.074; p < 0.001] and peritonitis (HR: 4.533; 95% CI: 1.748 to 11.751; p = 0.002) were risk factors for technique failure during the first 6 months, but BI≤7 was not correlated with technique failure. ♦ Conclusions: Patients starting PD with a break-in period of less than 1 week might experience a minor increased risk of mechanical complications, but no major effect on technique survival.

Intraperitoneal Interleukin-6 Levels Predict Peritoneal Solute Transport Rate: A Prospective Cohort Study

Background: To evaluate the association of dialysate interleukin-6 (IL-6), a marker of ongoing peritoneal inflammation, with the alteration of peritoneal solute transport rate (PSTR) in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: Stable CAPD patients were enrolled in the present study. A total of 128 patients were analyzed in this prospective study. IL-6 concentration in the overnight effluent was determined and expressed as the IL-6 appearance rate (IL-6AR). Mass transfer area coefficients of creatinine (MTACcr) were measured at enrollment and 12 months later. Logistic regression was used to examine the association between IL-6AR and change in MTACcr. Results: Multivariable linear regression showed that historical glucose exposure was significantly associated with dialysate IL-6AR level [β = 0.008 (0.001-0.015), p = 0.021]. After 12 months, MTACcr was significantly increased [6.40 (4.70-8.75) vs. 7.14 (5.69-8.73) ml/min, p = 0.004], while ultrafiltration capacity decreased [4 h UF 340 (220-400) vs. 280 (180-380) ml, p = 0.006]. Compared to the patients with stable PSTR, the dialysate IL-6AR in patients with increasing PSTR was significantly higher [277.08 (247.45-349.53) vs. 263.18 (69.94-286.72) pg/min, p = 0.015]. Patients with increasing PSTR had lower residual renal function [0.79 (0-2.12) vs. 1.70 (0.39-3.38) ml/min, p = 0.006] and less urine output [225 (0-600) vs. 500 (125-900) ml/24 h, p = 0.014]. Logistic analysis showed that both high dialysate IL-6AR [OR 1.333 and 95% CI (1.024-1.735), p = 0.033] and low RRF [OR 0.831 and 95% CI (0.699-0.988), p = 0.036] were independent risk factors for increasing PSTR. Conclusions: This prospective study suggests that intraperitoneal IL-6 is a predictor of increasing PSTR in peritoneal dialysis patients.

Angiopoietin-2/Tie2 signaling involved in TNF-α induced peritoneal angiogenesis.

PURPOSE Angiopoietin-2/Tie2 signaling has been found to play an important role in producing a vasculature in a variety of conditions. However, whether angiopoietin-2/Tie2 signaling is involved in peritoneal angiogenesis induced by TNF-α is not clear. In this study, we investigated the role of TNF-α on the function of human omental tissue microvascular endothelial cells (HOTMECs) and whether angiogenesis is inhibited by blocking angiopoietin-2/Tie2 signaling. METHODS Primary cultured HOTMECs were exposed to complete medium as control, medium containing 10 ng/ml TNF-α, a mixture of 10 ng/ml TNF-α plus 2 µg/ml sTie2/Fc or 2 µg/ml sTie2/Fc alone, respectively, as experimental groups. The proliferation of HOTMECs was measured by MTT assay. Expression of vascular endothelial growth factor (VEGF), Angiopoietin-2, and Tie2 were assessed by real-time PCR. We also investigated the angiogenesis of the HOTMECs by tube formation assay, their migration as well as their permeability to FITC-labeled BSA. RESULTS Compared to the cells in control, exposure to TNF-α or sTie2/Fc had no effect on proliferation of HOTMECs. TNF-α up-regulated the gene expression of VEGF, Angiopoietin-2, and Tie2 (p<0.05). TNF-α significantly promoted tube formation, migration and enhanced permeability of HOTMECs (p<0.05). Supplement with sTie2/Fc partially inhibited tube formation and migration (p<0.05). However, sTie2/Fc did not inhibit the increased permeability induced by TNF-α (p>0.05). CONCLUSIONS Angiopoietin-2/Tie2 signaling involved in TNF-α induced peritoneal angiogenesis may provide an alternative way to prevent peritoneal angiogenesis.

Interleukin-6 trans-signaling induces VEGF synthesis partly via Janus kinases-STAT3 pathway in human mesothelial cells.

Interleukin‐6 (IL‐6) is a vital inflammatory factor in the peritoneal cavity of peritoneal dialysis (PD) patients. Because intraperitoneal inflammation is closely associated with angiogenesis, we sought to explore the effect of IL‐6 on vascular endothelial growth factor (VEGF) synthesis and its transduction pathway in mesothelial cells.

Interleukin-6 trans-signalling induces vascular endothelial growth factor synthesis partly via Janus kinases-STAT3 pathway in human mesothelial cells

Interleukin‐6 (IL‐6) is a vital inflammatory factor in the peritoneal cavity of peritoneal dialysis (PD) patients. Because intraperitoneal inflammation is closely associated with angiogenesis, we sought to explore the effect of IL‐6 on vascular endothelial growth factor (VEGF) synthesis and its transduction pathway in mesothelial cells.