Impact of Weight Gain on the Subsequent Survival of New Peritoneal Dialysis Patients.

Introduction: Obesity at the initiation of dialysis was reported to adversely affect the clinical outcome of peritoneal dialysis (PD) patients, and weight gain is common after started on PD. However, there are few studies on the prognostic implications of weight gain after PD. Methods: We reviewed the change in body weight of 954 consecutive patients during the first 2 years of PD in a single Hong Kong center. Their subsequent clinical outcomes, including patient and technique survival rates, hospitalization, and peritonitis rates, were analyzed. Results: The mean age was 60.3 ± 12.2 years; 535 patients (56.1%) were men, and 504 (52.8%) had diabetes. From 1995-1999 to 2015-2019, the percentage of body weight gain during the first 2 years of PD was 1.0 ± 7.9%, 1.6 ± 7.1%, 1.6 ± 7.2%, 3.9 ± 9.5%, and 4.0 ± 10.3% for each 5-year period, respectively (p for linearity <0.0001). The subsequent 5-year patient survival rates were 29.9%, 43.3%, 40.5%, 43.6%, and 43.3% for patients with weight loss >5%, weight loss 2-5%, weight change with ±2%, weight gain 2-5%, and weight gain >5% during the first 2 years on PD, respectively (log-rank test, p = 0.035). With multivariable Cox regression model to adjust for clinical confounders, weight loss >5% during the first 2 years of PD was associated with a worse patient survival rate subsequently (adjusted hazard ratio 4.118, 95% confidence interval 1.040-16.313, p = 0.044), while weight gain was not associated with subsequent patient survival. Weight change during the first 2 years of PD does not appear to affect subsequent technique survival, hospitalization, decline in residual renal function, or peritonitis rate. Discussion and Conclusions: Weight gain is common during the first 2 years of PD, but weight gain does not appear to have any significant impact on the subsequent outcome. In contrast, weight loss >5% was significantly associated with worse patient survival subsequently.

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.

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.

Adipose and Plasma microRNAs miR-221 and 222 Associate with Obesity, Insulin Resistance, and New Onset Diabetes after Peritoneal Dialysis.

BACKGROUND: The correlation between microRNA, obesity, and glycemic intolerance in patients on peritoneal dialysis (PD) is unknown. We aimed to measure the adipose and plasma miR-221 and -222 levels, and to evaluate their association with adiposity, glucose intolerance, and new onset diabetes mellitus (NODM) after the commencement of PD. METHODS: We prospectively recruited incident adult PD patients. miR-221 and -222 were measured from adipose tissue and plasma obtained during PD catheter insertion. These patients were followed for 24 months, and the outcomes were changes in adiposity, insulin resistance, and NODM after PD. RESULTS: One hundred and sixty-five patients were recruited. Patients with pre-existing DM had higher adipose miR-221 (1.1 ± 1.2 vs. 0.7 ± 0.9-fold, p = 0.02) and -222 (1.9 ± 2.0 vs. 1.2 ± 1.3-fold, p = 0.01). High adipose miR-221 and -222 levels were associated with a greater increase in waist circumference (miR-221: beta 1.82, 95% CI 0.57-3.07, p = 0.005; miR-222: beta 1.35, 95% CI 0.08-2.63, p = 0.038), Homeostatic Model Assessment for Insulin Resistance (HOMA) index (miR-221: beta 8.16, 95% CI 2.80-13.53, p = 0.003; miR-222: beta 6.59, 95% CI 1.13-12.05, p = 0.018), and insulin requirements (miR-221: beta 0.05, 95% CI 0.006-0.09, p = 0.02; miR-222: beta 0.06, 95% CI 0.02-0.11, p = 0.002) after PD. The plasma miR-222 level predicted the onset of NODM (OR 8.25, 95% CI 1.35-50.5, p = 0.02). CONCLUSION: miR-221 and -222 are associated with the progression of obesity, insulin resistance, and NODM after 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.

Adipose and serum zinc alpha-2-glycoprotein (ZAG) expressions predict longitudinal change of adiposity, wasting and predict survival in dialysis patients.

There were limited data on adipose and serum zinc alpha-2-glycoprotein (ZAG) expression and its association with body composition in patients with advanced chronic kidney disease (CKD). This study aimed to quantify adipose and serum ZAG expression and evaluate their association with body composition and its longitudinal change, together with mortality in incident dialysis patients. We performed a single-center prospective cohort study. Patients who were planned for peritoneal dialysis were recruited. ZAG levels were measured from serum sample, subcutaneous and pre-peritoneal fat tissue obtained during peritoneal dialysis catheter insertion. Body composition and functional state were evaluated by bioimpedance spectroscopy and Clinical Frailty Scale respectively at baseline and were repeated 1 year later. Primary outcome was 2-year survival. Secondary outcomes were longitudinal changes of body composition. At baseline, the average adipose and serum ZAG expression was 13.4 ± 130.0-fold and 74.7 ± 20.9 µg/ml respectively. Both adipose and serum ZAG expressions independently predicted adipose tissue mass (ATM) (p = 0.001, p = 0.008, respectively). At 1 year, ATM increased by 3.3 ± 7.4 kg (p < 0.001) while lean tissue mass (LTM) remained similar (p = 0.5). Adipose but not serum ZAG level predicted change in ATM (p = 0.007) and LTM (p = 0.01). Serum ZAG level predicted overall survival (p = 0.005) and risk of infection-related death (p = 0.045) after adjusting for confounders. In conclusion, adipose and serum ZAG levels negatively correlated with adiposity and predicted its longitudinal change of fat and lean tissue mass, whilst serum ZAG predicted survival independent of body mass in advanced CKD patient.

The change in the prevalence of obesity and new-onset diabetes in Chinese peritoneal dialysis patients over 25 years.

BACKGROUND: The global prevalence of both obesity and end-stage kidney diseases (ESKDs) has increased in recent decades. Given the complicated interaction between obesity and ESKD, we examined the change in the prevalence of obesity in incident Chinese peritoneal dialysis (PD) patients over the past 25 years. METHODS: We reviewed the anthropometric measures of incident PD patients in a single Hong Kong center from 1995 to 2019. The results are reported in five 5-year periods. Patients with and without diabetes were analyzed separately, and the incidence of new-onset diabetes after PD was explored. RESULTS: We reviewed 1681 patients. Their mean age was 58.4 ± 12.5 years; 931 patients (55.4%) had pre-existing diabetes. From 1995-99 to 2015-19, the prevalence of obesity or overweight at the initiation of PD increased progressively for every 5-year period (from 21.9% to 26.2, 37.9, 42.7 and 47.3%, P < 0.001 for linearity). The increase in the prevalence of obesity or overweight was more pronounced in diabetic patients (from 33.7% to 59.6%) than non-diabetic ones (from 13.2% to 32.3%). Among nondiabetics patients, the incidence of new-onset diabetes after started on PD showed an insignificant rising trend during that period (from 18.0, 19.7, 17.8 and 22.4% to 23.3%, P = 0.106). The incidence of new-onset impaired fasting glucose or diabetes was significantly higher in obese or overweight patients than the others (56.9% versus 51.4%, P < 0.001). CONCLUSIONS: The prevalence of obesity has increased substantially in both diabetic and nondiabetic new PD patients in Hong Kong over the past 25 years. The incidence of new-onset diabetes was significantly higher in new PD patients with pre-existing obesity or overweight than those without obesity. The prognostic implication and impacts on the healthcare system deserve further studies.

Obesity, Weight Gain, and Fluid Overload in Peritoneal Dialysis.

Obesity is a global epidemic that has a complicated pathogenesis as well as impact on the outcome of peritoneal dialysis (PD) patients. In this review, the prevalence of obesity in incident PD patients as well as the phenomenon of new-onset glucose intolerance after PD will be reviewed. Published literature on the effect of obesity on the survival and incidence of cardiovascular disease in PD patients will be discussed. Particular emphasis would be put on literature that compared the impact of obesity on the outcome of hemodialysis and PD, and the confounding effect of dialysis adequacy. Next, the complex concept of obesity and its relevance for PD will be explored. The focus would be put on the methods of assessment and clinical relevance of central versus general obesity, as well as visceral versus subcutaneous adipose tissue. The relation between obesity and systemic inflammation, as well as the biological role of several selected adipokines will be reviewed. The confounding effects of metabolic syndrome and insulin resistance will be discussed, followed by the prevalence and prognostic impact of weight gain during the first few years of PD. The differences between weight gain due to fluid overload and accumulation of adipose tissue will be discussed, followed by the current literature on the change in body composition after patients are put on chronic PD. The methods of body composition will be reviewed, and the clinical relevance of individual body component (fluid, fat, muscle, and bone) will be discussed. The review will conclude by highlighting current gaps of knowledge and further research directions in this area.

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.

Prognostic significance of peritoneal dialysis effluent mitochondrial DNA level.

BACKGROUND: Mitochondrial DNA (mtDNA) resembles bacterial DNA and potentially triggers local and systemic inflammation. We evaluate the prognostic implications of PD effluent mtDNA level in peritoneal dialysis (PD) patients. METHODS: We measured mtDNA in the PD effluent (PDE) sediment and supernatant of 168 incident PD patients. All patients were followed for hospitalization, technique and overall survival. RESULTS: The median PD effluent supernatant and sediment mtDNA levels were 255.4 unit (interquartile range [IQR] 157.5-451.3) and 201.6 unit (IQR 147.8-267.3), respectively. Serum C-reactive protein level closely with PDE sediment mtDNA level (r = 0.471, p < 0.001) and less with supernatant mtDNA level (r = 0.156, p = 0.044). PDE supernatant mtDNA level correlates with dialysate-to-plasma creatinine ratio at 4 h (D/P4) (r = 0.361, p < 0.001) but not with any clinical outcome. PDE sediment mtDNA was an independent predictor of technique survival (p = 0.011) and the duration of hospitalization (p = 0.044) after adjusting for clinical confounding factors. CONCLUSIONS: PDE sediment mtDNA level significantly correlated with systemic inflammation, while PDE supernatant mtDNA level correlated with peritoneal transport. PDE sediment mtDNA level also independently predicted technique survival and duration of hospitalization. The mechanism of the different implications between PDE sediment and supernatant mtDNA levels deserves further investigations.