Relationship between Serial Serum Neutrophil-Lymphocyte Ratio, Cardiovascular Mortality, and All-Cause Mortality in Chinese Peritoneal Dialysis Patients.

INTRODUCTION: It is believed that the excessive cardiovascular (CV) burden of patients on peritoneal dialysis (PD) is closely associated with chronic inflammation. Neutrophil-lymphocyte ratio (NLR) is an inflammatory marker that was shown to correlate with CV outcomes. However, little is known about the significance of serial monitoring of serum NLR. We aimed to determine the prognostic value of serial NLR on all-cause mortality and CV mortality in PD patients. METHODS: Serial measurement of NLR was obtained from 225 incident PD patients in a single center, with each measurement 1 year apart. Patients were divided into two groups ("high" vs. "low") by the median value of NLR. The primary and secondary outcome measure was all-cause and CV mortality, respectively. RESULTS: After a median of follow-up for 43.9 months, patients with lower baseline NLR demonstrated a higher survival rate (p = 0.01). Patients with persistently high NLR values on serial measurement had the lowest survival rate (p = 0.03). Multivariate Cox regression showed that this group of patients had significantly higher all-cause mortality (HR: 1.74, 95% CI: 1.09-2.79, p = 0.02). However, the NLR failed to demonstrate a statistically significant relationship with CV mortality. CONCLUSIONS: While baseline NLR was an independent predictor of all-cause mortality in PD patients, persistent elevation in NLR appeared to further amplify the risk. Regular monitoring of serial serum NLR may enable early identification of patients who are at risk of adverse outcome.

Plasma vaspin levels and clinical outcome in incident peritoneal dialysis patients.

BACKGROUND: Vaspin is an adipokine that regulates glucose and lipid metabolism. Plasma vaspin level is increased in chronic kidney disease but decreased in hemodialysis patients. However, plasma vaspin level in peritoneal dialysis (PD) patients, as well as its prognostic role, has not been studied. METHODS: We recruited 146 incident PD patients. Their baseline plasma vaspin levels, body anthropometry, the profile of insulin resistance, bioimpedance spectroscopy parameters, dialysis adequacy, and nutritional indices were measured. They were followed for up to 5 years for survival analysis. RESULTS: The average age was 58.4 ± 11.8 years; 96 patients (65.8%) were men, and 90 (61.6%) had diabetes. The median vaspin level was 0.18 ng/dL (interquartile range [IQR] 0.11 to 0.30 ng/dL). Plasma vaspin level did not have a significant correlation with adipose tissue mass or baseline insulin level. However, plasma vaspin level had a modest correlation with the change in insulin resistance, as represented by the HOMA-IR index, in non-diabetic patients (r = -0.358, p = 0.048). Although the plasma vaspin level quartile did not have a significant association with patient survival in the entire cohort, it had a significant interaction with diabetic status (p < 0.001). In nondiabetic patients, plasma vaspin level quartile was an independent predictor of patient survival after adjusting for confounding clinical factors (adjusted hazard ratio 2.038, 95% confidence interval 1.191-3.487, p = 0.009), while the result for diabetic patients was not significant. CONCLUSIONS: Plasma vaspin level quartile had a significant association with patient survival in non-diabetic PD patients. Baseline plasma vaspin level also had a modest inverse correlation with the subsequent change in the severity of insulin resistance, but the exact biological role of vaspin deserves further studies.

Adipose expression of miR-130b and miR-17-5p with wasting, cardiovascular event and mortality in advanced chronic kidney disease patients.

BACKGROUND: There are limited data on the association of adipose microRNA expression with body composition and adverse clinical outcomes in patients with advanced chronic kidney disease (CKD). We aimed to evaluate the association of adipose miR-130b and miR-17-5p expressions with body composition, functional state, cardiovascular outcome and mortality in incident dialysis patients. METHODS: We performed a single-center prospective cohort study. Patients who were planned for peritoneal dialysis were recruited. miR-130b and miR-17-5p expressions were measured from subcutaneous and pre-peritoneal fat tissue obtained during peritoneal dialysis catheter insertion. Body composition and physical function were assessed by bioimpedance spectroscopy and Clinical Frailty Scale. Primary outcome was 2-year survival. Secondary outcomes were 2-year technique survival and major adverse cardiovascular event (MACE) rate. RESULTS: Adipose expression of miR-130b and miR-17-5p correlated with parameters of muscle mass including intracellular water (miR-130b: r = 0.191, P = 0.02; miR-17-5p: r = 0.211, P = 0.013) and lean tissue mass (miR-17-5p: r = 0.176, P = 0.04; miR-17-5p: r = 0.176, P = 0.004). miR-130b expression predicted frailty significantly (P = 0.017). Adipose miR-17-5p expression predicted 2-year all-cause survival (P = 0.020) and technique survival (P = 0.036), while miR-130b expression predicted incidence of MACE (P = 0.015). CONCLUSIONS: Adipose miR-130b and miR-17-5p expressions correlated with body composition parameters, frailty, and predicted cardiovascular events and mortality in advanced CKD patients.

Progression in Physical Frailty in Peritoneal Dialysis Patients.

BACKGROUND: Physical frailty contributes to adverse clinical outcomes in peritoneal dialysis (PD) patients. Little has been reported about frailty transitions in this population. We aimed to describe the transitions of frailty in PD patients and identify factors that predicted changes in frailty state. METHODS: In a prospective observational study, we recruited 267 PD patients. Frailty was assessed by a validated frailty score. Depression was graded by PHQ-9 score, and nutritional status was evaluated by serum albumin, Subjective Global Assessment (SGA), and comprehensive Malnutrition Inflammation Score (MIS). The primary outcome was the change in frailty score at follow-up compared to baseline. RESULTS: At baseline, 194 (72.7%) patients were classified as frail. With time, their frailty scores significantly increased (p < 0.001), and 93 of the surviving subjects (78.2%) were classified as frail. There was a modest significant correlation between change in MIS (p < 0.001), change in SGA score (p < 0.001), and change in PHQ-9 score (p < 0.001) with change in frailty score. An increase in PHQ-9 score (p < 0.001) and MIS (p = 0.001), as well as longer duration of hospitalization (p = 0.001), was independently associated with a greater change in frailty score after adjustment for confounding factors. Frailty score was also improved in patients who were converted to hemodialysis (p = 0.048) and received renal transplantation (p = 0.005). CONCLUSION: Our findings suggested that frailty transitions were common in PD patients. Worsening in nutrition and depression, together with a longer duration of hospitalization, were associated with worsening in frailty.

Depression does not predict clinical outcome of Chinese peritoneal Dialysis patients after adjusting for the degree of frailty.

BACKGROUND: Depression and frailty contribute to the adverse clinical outcome of peritoneal dialysis (PD) patients. However, the interaction between depression and frailty in PD patients remains uncertain. We determined the prevalence of depression and frailty in prevalent Chinese PD patients, dissected the internal relationship between depression and frailty, and determined their relative contribution to the adverse clinical outcome in PD patients. METHODS: In a prospective observational study, we recruited 267 prevalent PD patients. Depression was identified by Patient Health Questionnaire (PHQ-9). Frailty was identified by a validated Frailty Score. All cases were followed for one year. Outcome measures included number and duration of hospitalization, peritonitis rate, and all-cause mortality. RESULTS: Of the 267 patients, 197 patients (73.8%) were depressed, and 157 (58.8%) were frail. There was a substantial overlap between depression and frailty. Although depression and frailty were associated the number and duration of hospitalization by univariate analysis, the association became insignificant after adjusting for confounding factors by multivariate analysis. Both depression and frailty were associated with one-year mortality by univariate analysis. One-year patient survival was 95.9, 86.5, 82.4 and 71.0% for patients with nil, mild, moderate and severe frailty, respectively (p = 0.001). Frailty was an independent predictor of patient survival by multivariate analysis (adjusted hazard ratio 1.424, 95% confidence interval 1.011-2.005. p = 0.043), while the prognostic effect of depression disappears after adjusting for frailty score. CONCLUSION: Depression and frailty were common among Chinese PD patients. Frailty, but not depression, was an independent predictor of one-year mortality.

The efficacy of managing fluid overload in chronic peritoneal dialysis patients by a structured nurse-led intervention protocol.

BACKGROUND: Extracellular volume overload is a common problem in peritoneal dialysis (PD) patients and is associated with excessive mortality. We determine the effectiveness of treating PD patients with extracellular volume overload by a structured nurse-led intervention program. METHODS: The hydration status of PD patients was screened by bioimpedance spectroscopy (BIS). Fluid overload was defined as overhydration volume ≥ 2 L. Patients were classified into Symptomatic and Asymptomatic Groups and were managed by a structured nurse-led intervention protocol that focused on education and motivation. Hypertonic cycles were given for short term symptom relief for the Symptomatic group. Patients were followed for 12 weeks for the change in volume status, blood pressure, knowledge and adherence as determined by standard questionnaires. RESULTS: We recruited 103 patients (53 Symptomatic, 50 Asymptomatic Group. There was a significant reduction in overhydration volume 4 weeks after intervention, which was sustained by week 12; the overall reduction in overhydration volume was 0.96 ± 1.43 L at 4 weeks, and 1.06 ± 1.70 L at 12 weeks (p < 0.001 for both). The improvement was significant for both Symptomatic and Asymptomatic Groups. There was a concomitant reduction in systolic blood pressure in the Asymptomatic (146.9 ± 20.7 to 136.9 ± 19.5 mmHg, p = 0.037) but not Symptomatic group. The scores of knowledge, adherence to dietary control and advices on daily habit at week 4 were all significantly increased, and the improvement was sustained at week 12. CONCLUSIONS: The structured nurse-led intervention protocol has a lasting benefit on the volume status of PD patients with extracellular volume overload. BIS screening allows prompt identification of volume overload in asymptomatic patients, and facilitates a focused effort on this high risk group.

Urinary mitochondrial DNA level is an indicator of intra-renal mitochondrial depletion and renal scarring in diabetic nephropathy.

Background: Mitochondrial dysfunction plays an important role in the pathogenesis and progression of diabetic nephropathy (DN). We study the relation between urinary and intra-renal mitochondrial deoxyribonucleic acid (mtDNA) levels and renal dysfunction in DN. Methods: We recruited 92 patients with biopsy-proven DN. Urinary sediment, urinary supernatant and intra-renal mtDNA levels were measured and compared with baseline renal biopsy, kidney scarring and renal function decline in the subsequent 24 months. Results: mtDNA could be detected in all urine supernatant, urine sediment and renal biopsy specimens. There was a modest but statistically significant inverse correlation between urinary supernatant and intra-renal mtDNA levels (r = -0.453, P = 0.012). Urinary supernatant mtDNA level had modest but statistically significant correlations, inversely with estimated glomerular filtration rate (r = -0.214, P = 0.04), and positively with interstitial fibrosis (r = 0.300, P = 0.005). Intra-renal mtDNA had significant inverse correlation with interstitial fibrosis (r = -0.537, P = 0.003). However, there was no significant relation between renal function decline and urinary supernatant, urinary sediment or intra-renal mtDNA levels. Conclusions: mtDNA is readily detectable in urinary supernatant and kidney tissue, and their levels correlate with renal function and scarring in DN. Further studies are needed to determine the accuracy of urinary supernatant mtDNA level as a prognostic indicator of DN, as well as its role in other kidney diseases.

Depression and Physical Frailty Have Additive Effect on the Nutritional Status and Clinical Outcome of Chinese Peritoneal Dialysis.

BACKGROUND/AIMS: Frailty and depression both contribute to malnutrition and adverse clinical outcome of peritoneal dialysis (PD) patients. However, their interaction is incompletely defined. METHODS: We studied 178 adult Chinese PD patients. Physical frailty was assessed by a validated in-house questionnaire; depressive symptoms was screened by the Geriatric Depression Scale; nutritional status was determined by subjective global assessment (SGA) and malnutrition inflammation score (MIS). All patients were followed for up to 24 months for survival and hospitalization analysis. RESULTS: There were 111 patients (62.4%) physically frail, amongst those 48 (43.2%) had depressive symptoms. Only 1 patient had depressive symptoms without frailty. There was an additive effect of depressive symptoms and physical frailty on nutritional status. For the groups with no frailty, frail but no depressive symptoms, and frail with depressive symptoms, serum albumin decreased in a stepwise manner (35.8 ± 5.6, 34.9 ± 4.4, and 32.9 ± 5.3 g/L, respectively, p=0.025); overall SGA score was 5.75 ± 0.61, 5.41 ± 0.59, and 5.04 ± 0.77, respectively (p< 0.0001), and MIS was 5.12 ± 2.30, 7.13 ± 3.22, and 9.48 ± 3.97, respectively (p< 0.0001). At 24 months, patient survival was 86.6%, 71.4%, and 62.5% for patients with no frailty, frail but no depressive symptoms, and frail with depressive symptoms, respective (p=0.001). The median number of hospital stay was 8.04 (inter-quartile range [IQR] 0.91 - 19.42), 14.05 (IQR 3.57 - 37.27), and 26.62 (IQR 10.65 - 61.18) days per year of follow up, respectively (p< 0.0001). CONCLUSION: Physical frailty and depressive symptoms are both common in Chinese PD patients, and they have additive adverse effect on the nutritional status and clinical outcome.

Urinary mitochondrial DNA level as a biomarker of tissue injury in non-diabetic chronic kidney diseases.

BACKGROUND: Urinary mitochondrial DNA (mtDNA) fragment level has been proposed as a biomarker of chronic kidney disease (CKD). In this study, we determine the relation between urinary mtDNA level and rate of renal function deterioration in non-diabetic CKD. METHODS: We recruited 102 non-diabetic CKD patients (43 with kidney biopsy that showed non-specific nephrosclerosis). Urinary mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 48.3 ± 31.8 months for renal events (need of dialysis or over 30% reduction in estimated glomerular filtration rate [eGFR]). RESULTS: The median urinary mtDNA level was 1519.42 (inter-quartile range 511.81-3073.03) million copy/mmol creatinine. There were significant correlations between urinary mtDNA level and baseline eGFR (r = 0.429, p < 0.001), proteinuria (r = 0.368, p < 0.001), severity of glomerulosclerosis (r = - 0.537, p < 0.001), and tubulointerstitial fibrosis (r = - 0.374, p = 0.014). The overall rate of eGFR decline was - 2.18 ± 5.94 ml/min/1.73m2 per year. There was no significant correlation between the rate of eGFR decline and urinary mtDNA level. By univariate analysis, urinary mtDNA level predicts dialysis-free survival, but the result became insignificant after adjusting for clinical and histological confounding factors. CONCLUSION: Urinary mtDNA levels have no significant association with the rate of renal function decline in non-diabetic CKD, although the levels correlate with baseline renal function, proteinuria, and the severity of histological damage. Urinary mtDNA level may be a surrogate marker of permanent renal damage in non-diabetic CKD.

Plasma Mitochondrial DNA Level is a Prognostic Marker in Peritoneal Dialysis Patients.

BACKGROUND/AIMS: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that circulating mitochondrial DNA, which has a similar structure with bacterial DNA, correlates with systemic inflammatory state and predicts cardiovascular event in new PD patients. METHODS: We measured plasma mitochondrial DNA level by quantitative polymerase chain reaction (PCR) in 197 new PD patients and 150 patients with chronic kidney disease. PD patients were followed for 24 months for the development of cardiovascular event, hospitalization, and patient survival. RESULTS: There was a stepwise increase in plasma mitochondrial DNA level with worsening renal function. The average plasma mitochondrial DNA level was 18.0 ± 1.2 PCR cycles. Plasma mitochondrial DNA level correlated with serum CRP level (r = -0.538, p < 0.0001). At 24 months, the event-free survival was 67.4%, 66.4%, 63.4% and 44.2% for plasma mitochondrial DNA level quartiles I, II, III and IV, respectively (p = 0.049). After adjusting for confounders, plasma mitochondrial DNA level, malnutrition-inflammation score, and baseline arterial pulse wave velocity were independent predictors of composite cardiovascular end-point; each doubling in plasma mitochondrial DNA level confers 16.0% (95% confidence interval, 2.5 - 31.3%, p = 0.001) excess in risk. Plasma mitochondrial DNA also correlated with the number of hospital admission (r = -0.218, p = 0.002) and duration of hospitalization for cardiovascular reasons (r = -0.232, p = 0.001). CONCLUSION: Plasma mitochondrial DNA level significantly correlates with systemic inflammatory state, and is a strong predictor of cardiovascular event as well as the need of hospitalization in new PD patients.

Frailty in Chinese Peritoneal Dialysis Patients: Prevalence and Prognostic Significance.

BACKGROUND/AIMS: Previous studies showed that frailty is prevalent in both pre-dialysis and dialysis patients. However, the prevalence and prognostic implication of frailty in Chinese peritoneal dialysis (PD) patients remain unknown. METHODS: We used a validated questionnaire to determine the Frailty Score of 193 unselected prevalent PD patients. All patients were then followed for 2 years for their need of hospitalization and mortality. RESULTS: Amongst the 193 patients, 134 (69.4%) met the criteria of being frail. Frailty Score significantly correlated with Charlson's comorbidity score (r = 0.40, p < 0.0001), Malnutrition Inflammation Score (r = 0.59, p < 0.0001), and inversely with Subjective Global Assessment score (r = -0.44, p < 0.0001). Frailty was closely associated with the need of hospitalization. Patients with nil, mild, moderate, and severe frailty required 2.4 ± 6.0, 1.6 ± 1.6, 2.7 ± 2.5, 5.2 ± 4.8 hospital admissions per year, respectively (p < 0.0001), and they stayed in hospital for 6.4 ± 9.2, 5.3 ± 6.2, 10.0 ± 10.4, 12.9 ± 20.1 days per hospital admission, respectively (p < 0.0001). However, Frailty Score was not an independent predictor of patient or technique survival. CONCLUSIONS: Frailty is prevalent among Chinese PD patients. Frail PD patients have a high risk of requiring hospitalization and their hospital stay tends to be prolonged. Early identification may allow timely intervention to prevent adverse health outcomes in this group of patients.

Effect of cinacalcet treatment on vascular arterial stiffness among peritoneal dialysis patients with secondary hyperparathyroidism.

AIM: Although calcimimetics cinacalcet can reduce parathyroid hormone level and control secondary hyperparathyroidism in end-stage renal disease patients, risk of vascular calcification remains high. Whether cinacalcet can further reduce vascular damage or arterial stiffness is unknown. METHODS: We studied the effect of cinacalcet in 33 peritoneal dialysis patients with inadequately controlled secondary hyperparathyroidism despite standard treatment. The primary outcome was the aortic pulse wave velocity at 26 and 52 months after cinacalcet treatment. The pulse wave velocity was compared with that of a matched control cohort of 37 peritoneal dialysis patients with secondary hyperparathyroidism. RESULTS: Thirty-three patients completed the cinacalcet treatment, after median dialysis duration of 1.0 year. Significant improvement of parathyroid hormone level was achieved after 52 weeks, from 87.5 ± 28.7 pmol/L to 34.5 ± 45.5 pmol/L (P < 0.0001). Serial carotid-femoral pulse wave velocity did not differ between cinacalcet treatment group and control group (general linear model with repeated measures, P = 0.19). Among patients receiving cinacalcet, the average carotid-femoral pulse wave velocity increased from 10.46 ± 2.12 m/s at baseline to 11.41 ± 2.79 m/s at 52 weeks (P = 0.001). The change in carotid-femoral pulse wave velocity over 1 year had no significant correlation with the final parathyroid hormone level or change in parathyroid hormone level. CONCLUSIONS: Among prevalent patients receiving peritoneal dialysis and with hyperparathyroidism, a reduction of 60.6% parathyroid hormone level after cinacalcet treatment for one year did not reduce the carotid-femoral pulse wave velocity.

Circulating bacterial-derived DNA fragments as a marker of systemic inflammation in peritoneal dialysis.

BACKGROUND: Endotoxemia is common in peritoneal dialysis (PD) patients, and circulating lipopolysaccharide (LPS) level is related to the degree of systemic inflammation and atherosclerosis. We hypothesize that circulating bacterial DNA, another microbial component, correlates with the degree of systemic inflammation and predicts the survival of new PD patients. METHODS: We measured the plasma bacterial DNA level in the archive blood samples of 300 consecutive new PD patients. The result was compared with serum C-reactive protein (CRP) level, patient survival and peritonitis-free survival. RESULTS: The average age was 57.8 ± 12.1 years, average plasma bacterial DNA level 34.3 ± 1.3 cycles and average follow-up 37.9 ± 22.2 months. The plasma bacterial DNA level correlated with serum CRP (r = 0.565, P < 0.001) and LPS levels (r = 0.224, P = 0.029). At 36 months, the patient survival were 77.5, 78.3, 74.6 and 65.2% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (log-rank test, P = 0.034). By multivariate analysis with the Cox proportional hazard model to adjust for confounders, the plasma bacterial DNA level had no independent effect. Similarly, peritonitis-free survival were 60.6, 59.8, 60.3 and 50.4% for plasma bacterial DNA level quartiles I, II, III and IV, respectively, at 36 months (P = 0.020), and the difference was not significant after adjusting for confounding factors. CONCLUSION: We found that the plasma bacterial DNA level correlated with the degree of systemic inflammatory state in PD patients. Although plasma bacterial DNA level seems to predict patient survival and peritonitis-free survival, the association disappears after adjusting for confounding factors. Further prospective studies are needed to delineate the role of plasma bacterial DNA as a prognostic marker of renal failure patients.

Effect of using ultrapure dialysate for hemodialysis on the level of circulating bacterial fragment in renal failure patients.

BACKGROUND: Cardiovascular disease is the major cause of mortality and morbidity in dialysis patients. Recently, circulating endotoxin is found to associate with the systemic inflammatory state and cardiovascular disease of dialysis patients. Previous studies showed that the use of ultrapure dialysate for hemodialysis could reduce the exposure to exogenous endotoxin. We studied the effect of using ultrapure dialysate for hemodialysis on circulating endotoxin and bacterial DNA fragment levels and vascular stiffness. METHODS: This is an open-labeled prospective study of 25 patients (14 male). Circulating endotoxin and bacterial DNA level, vascular stiffness as represented by arterial pulse wave velocity (PWV), nutrition and hydration status were monitored before and repeatedly throughout 12 months after the use of ultrapure dialysate for hemodialysis. RESULTS: The average age was 58.9 ± 10.2 years; 21 patients completed the study. Within 4 weeks of conversion to ultrapure dialysate for hemodialysis, the plasma endotoxin level fell from 0.302 ± 0.083 to 0.209 ± 0.044 EU/ml (p < 0.0001) and then remained static, while serum bacterial DNA level remained similar. Furthermore, the time-averaged plasma endotoxin level during the study period significantly correlated with serum C-reactive protein level (r = 0.483, p = 0.017), carotid-femoral PWV (r = 0.455, p = 0.033), and malnutrition inflammation score (r = 0.461, p = 0.031). The time-averaged serum bacterial DNA level significantly correlated with malnutrition inflammation score (r = 0.550, p = 0.008) and inversely with subjective global assessment score (r = -0.543, p = 0.009), but not with PWV. CONCLUSIONS: In hemodialysis patients, circulating endotoxin level is associated with vascular stiffness and systemic inflammation. Using ultrapure dialysate for hemodialysis effectively reduces circulating endotoxin level in hemodialysis patients. The long-term benefit of using ultrapure dialysate for hemodialysis requires further study.

Dietary Micronutrient Intake and Its Relationship with the Malnutrition-Inflammation-Frailty Complex in Patients Undergoing Peritoneal Dialysis.

BACKGROUND: The relationship between dietary patterns and the malnutrition-inflammation-frailty complex in patients undergoing peritoneal dialysis (PD) is currently unknown. Our objective was to measure dietary nutrient intake and evaluate its association with malnutrition, inflammation, and frailty. METHODS: We prospectively recruited adult PD patients. We assessed their dietary nutrient intake using a food frequency questionnaire. Frailty, malnutrition, and inflammation were evaluated by validated Frailty Score (FQ), Subjective Global Assessment (SGA), and Malnutrition-Inflammation Score (MIS). RESULTS: A total of 209 patients were recruited for the study. Among them, 89 patients (42.6%) had an insufficient protein intake, and 104 patients (49.8%) had an insufficient energy intake. Additionally, 127 subjects were identified as frail, characterized by being older (61.9 ± 9.5 vs. 55.6 ± 12.8, p < 0.001), malnourished (SGA: 21.0 ± 2.7 vs. 22.7 ± 3.1, p < 0.001), and having a high inflammation burden (MIS: 10.55 ± 3.72 vs. 7.18 ± 3.61, p < 0.001). There was a significant correlation between dietary zinc intake and body mass index (r = 0.31, p < 0.001), SGA (r = 0.22, p = 0.01), and MIS (r = -0.22, p = 0.01). In the multivariate model, a higher dietary zinc intake predicted a higher SGA (beta 0.03, p = 0.003) and lower FQ (beta -0.38, p < 0.001) and MIS (beta -0.14, p < 0.001), indicating a better nutrition, less frail and inflamed state. A higher dietary zinc intake was also associated with a lower odds of being frail (adjusted odds ratio 0.96, p = 0.009). CONCLUSION: Dietary inadequacy and micronutrient deficiency are common among the PD population. Dietary zinc intake is independently associated with an improved nutrition, physical condition, and reduced inflammatory state.

Predictors and prognostic significance of persistent fluid overload: A longitudinal study in Chinese peritoneal dialysis patients.

BACKGROUND: Cross-sectional studies showed that fluid overload (FO) measured by bioimpedance spectroscopy (BIS) predicted adverse outcomes in patients on peritoneal dialysis (PD). We aimed to describe the longitudinal change in volume status in Chinese PD patients and determine its relation with clinical outcomes. METHODS: We performed a single-centre, retrospective analysis of all PD patients who underwent repeated BIS from 2010 to 2015. FO was defined by relative hydration index (RHI; volume of overhydration adjusted by extracellular water >7%). Variability of volume status (VVS) was denoted by the standard deviation of all RHI. The association of time-averaged RHI and VVS on patient and technique survival was explored by a competing risk model. RESULTS: A total of 269 patients were followed for a median of 47.1 months. Mean time-averaged RHI was 17.6 ± 10.2%. Multivariable mixed linear regression revealed that RHI was significantly associated with diabetes, time-varying systolic blood pressure, and inversely with time-varying albumin level, lean tissue index and fat tissue index (p <0.0001 for all). Time-averaged RHI independently predicted patient survival (subdistribution hazard ratio (SHR) 1.05, 95% CI 1.03-1.07, p <0.0001) and technique survival (SHR 1.04, 95% CI 1.02-1.06, p <0.0001), whereas VVS did not. The mortality risk for patients with persistent FO was consistently higher than the corresponding risk estimated from baseline FO of the same extent. CONCLUSIONS: Persistent FO was a strong predictor of patient and technique failure. Repeated bioimpedance measurements to monitor volume status may provide additional prognostic information in PD patients.

Pharmacokinetics of Apixaban Among Peritoneal Dialysis Patients.

Rationale & Objective: The efficacy and safety profile of apixaban remains uncertain in patients receiving peritoneal dialysis (PD) despite increasing use in this population. Accordingly, we assessed the pharmacokinetics of apixaban among patients receiving PD. Study Design: A pharmacokinetics study in a single center. Patients recruited received 1 week of apixaban at 2.5 mg twice a day to reach steady state. Serial blood samples were then taken before and after the last dose for pharmacokinetics analysis of apixaban. Setting & Participants: Ten stable PD patients with atrial fibrillation in an outpatient setting. Analytical Approach/Outcomes: Pharmacokinetic parameters including the area under the concentration-time curve from time 0 to 12 hours after the last dose of apixaban (AUC0-12), peak concentration, trough level, time to peak apixaban concentration, half-life, and drug clearance were analyzed. Results: There was a wide variation in the range of apixaban concentration across the 10 patients. The AUC0-12 for the PD group was significantly higher than those reported previously for hemodialysis patients or healthy individuals. Three patients had a supratherapeutic peak concentration whereas 2 patients had a supratherapeutic trough level as compared with the pharmacokinetic parameter in healthy individuals taking equivalent therapeutic dosage. Limitations: Small sample size with short study duration limits the ability to ascertain the true bleeding risk and to detect any clinical outcomes. Results may be limited to Asian populations only. Conclusions: A proportion of PD patients had supratherapeutic levels even when the reduced dosage 2.5 mg twice a day was used. Given the large interindividual variation in the drug level, therapeutic drug monitoring should be done if available. Otherwise, one should start the drug at reduced doses with caution and with more frequent clinical monitoring for any signs of bleeding.

Omentin-1 Levels and Outcomes in Incident Peritoneal Dialysis Patients.

Rationale & Objective: Omentin-1 is an adipokine with anti-inflammatory and cardioprotective properties. The objective of this study was to determine the prognostic role of plasma omentin-1 levels in incident peritoneal dialysis (PD) patients. Study Design: Retrospective analysis of prospective cohort. Setting & Participants: 152 incident PD patients. Predictors: Plasma omentin-1 level, adipose tissue omentin-1 messenger RNA (mRNA) expression. Outcomes: Patient survival, technique survival, hospital admission, and duration of stay. Analytical Approach: Time-to-event survival analyses; linear regression for hospitalization. Results: The mean age was 58.4 ± 11.7 years; 102 were men, and 92 had diabetes. There was no significant correlation between plasma omentin-1 level and its adipose tissue mRNA expression. A higher plasma omentin-1 level quartile was not associated with patient survival (P = 0.92) or technique survival (P = 0.83) but had a modest correlation with a lower number of hospital admissions (P = 0.07) and shorter duration of hospital stay (P = 0.04). In adjusted models using multivariable linear regression, a higher plasma omentin-1 level quartile remained significantly associated with fewer hospital admissions (ß, -0.13; 95% CI, -0.26 to -0.002; P = 0.05) and shorter hospitalization duration (ß, -0.20; 95% CI, -0.38 to -0.02; P = 0.03). Limitations: Observational study with baseline measures only. Conclusions: Plasma omentin-1 level was not associated with patient survival, technique survival, or peritonitis, but higher plasma omentin-1 levels were associated with fewer hospital admissions and shorter duration of hospitalization among incident PD patients.

Circulating and Adipose Tissue Adiponectin Level and Outcomes in Incident Peritoneal Dialysis Patients.

Rationale & Objective: Cardiovascular disease is the major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Adiponectin, a key adipokine, is related to obesity and insulin resistance. We determined the clinical and prognostic value of plasma adiponectin level and its adipose tissue messenger RNA (mRNA) expression in new PD patients. Study Design: Retrospective analysis of a prospective observational study. Setting & Participants: 152 new PD patients from a single center; 6 adults undergoing abdominal surgeries without kidney disease served as controls. Predictors: Plasma adiponectin level and its adipose tissue mRNA expression. Outcomes: Body build and composition, patient and technique survival. Analytical Approach: Adiponectin level and mRNA expression were grouped in quartiles for correlation analysis for body build and Cox regression for survival analysis. Results: The median plasma adiponectin level was 31.98 µg/mL (IQR, 16.81-49.49 µg/mL), and adiponectin mRNA expression in adipose tissue was 1.65 times higher than in controls (IQR, 0.98-2.63). There was a modest but statistically significant correlation between plasma adiponectin and its adipose tissue mRNA expression (r = 0.40, P < 0.001). Plasma adiponectin level inversely correlated with body mass index, waist-hip ratio, mid-arm circumference, adipose tissue mass, plasma triglyceride (r = -0.39, -0.38, -0.41, -0.38, and -0.30, respectively; P < 0.001 for all), as well as serum insulin level (r = -0.24, P = 0.005). Similar correlations were present but less marked with adipose tissue adiponectin mRNA level. Neither plasma adiponectin level nor adipose tissue adiponectin mRNA level predicted patient or technique survival. Limitations: Observational study, single center, single baseline measurement. Conclusions: Plasma adiponectin level correlated with the degree of adiposity in new PD patients. However, neither plasma adiponectin level nor its adipose tissue mRNA expression was an independent prognostic indicator in kidney failure patients newly started on PD.

The Impact of Volume Overload on the Longitudinal Change of Adipose and Lean Tissue Mass in Incident Chinese Peritoneal Dialysis Patients.

Patients treated with peritoneal dialysis (PD) experience complex body composition changes that are not adequately reflected by traditional anthropometric parameters. While lean and adipose tissue mass can be readily assessed by bioimpedance spectroscopy (BIS), there is concern about the potential confounding effect of volume overload on these measurements. This study aimed to assess the influence of fluid status (by echocardiography) on body composition parameters measured by BIS and to describe the longitudinal changes in adipose and lean tissue mass. We conducted a prospective observational study in a tertiary hospital. Incident Chinese PD patients underwent baseline echocardiography and repeated BIS measurements at baseline and 12 months later. Among 101 PD patients, lean tissue index (LTI) or fat tissue index (FTI) was not associated with echocardiographic parameters that reflected left ventricular filling pressure (surrogate of volume status). Sixty-eight patients with repeated BIS had a significant increase in body weight and FTI, while LTI remained similar. Gains in fat mass were significantly associated with muscle wasting (beta = −0.71, p < 0.0001). Moreover, progressive fluid accumulation independently predicted decrease in FTI (beta = −0.35, p < 0.0001) but not LTI. Body composition assessments by BIS were not affected by fluid status and should be considered as part of comprehensive nutrition assessment in PD patients.