Abstract
Confounding Effect of Malnutrition and Comorbidities on Survival of Continuous Ambulatory Peritoneal Dialysis Patients
Objectives: To analyze confounding effect of comorbidities (CMDs) and malnutrition (MN) on survival of continuous ambulatory peritoneal dialysis (CAPD) patients (pts).
Methods: In this study, 342 CAPD pts (179 with diabetes; 250 men; mean age: 51 years) were followed for 22 patient–months (pt-mos). Based on subjective global assessment (SGA) and CMDs, pts were categorized into four groups: normal nutrition (NN) with CMD [n = 26 (7.6%)]; NN without CMD [n = 61 (17.8%)]; MN with CMD [n = 160 (46.8%)]; and MN without CMD [n = 95 (27.8%)]. Kaplan–Meier analysis was used to compare survival in the various groups. Univariate and multivariate Cox regression analysis was used to analyze predictors of patient survival.
Results: Based on SGA, 87 pts (25.4%) had NN, 229 (66.9%) had mild-to-moderate MN, and 26 (7.6%) had severe MN. Mean survival in pts with NN (58 pt–mos) was greater than in pts with MN (42 pt–mos, p = 0.0002). Mean survival in pts with CMD (39 pt–mos) was inferior to that in pts without CMD (55 pt–mos, p = 0.0001). The mean actuarial survival was 46 pt–mos in NN with CMD; 62 pt–mos in NN without CMD; 37 pt–mos in MN with CMD; and 46 pt–mos in MN without CMD, p = 0.0001.
On univariate Cox regression analysis, CMD [p = 0.001; odds ratio (OR): 0.33; 95% confidence interval (CI): 0.21 to 0.53], age (p = 0.001; OR: 0.95; 95% CI: 0.60 to 1.50), nutrition status (p = 0.001; OR: 0.32; 95% CI: 0.17 to 0.61), serum albumin (p = 0.02; OR: 0.66; 95% CI: 0.46 to 0.94), residual glomerular filtration rate [rGFR (p = 0.001; OR: 0.87; 95% CI: 0.81 to 0.93)], and diabetes status (p = 0.001; OR: 2.24; 95% CI: 1.54 to 3.79) were significant predictors of survival. Adequacy of dialysis [Kt/V (p = 0.09; OR: 0.41; 95% CI: 0.14 to 1.1)] and peritonitis (p = 0.55; OR: 0.88; 95% CI: 0.57 to 1.13) were not predictors of survival. On multivariate analysis, only CMD (p = 0.001; OR: 0.41; 95% CI: 0.25 to 0.67), nutrition status (p = 0.01; OR: 0.44; 95% CI: 0.23 to 0.85), and rGFR (p = 0.003; OR: 0.90; 95% CI: 0.84 to 0.96) were significant predictors of survival in these pts. On time-dependent multivariate Cox regression analysis, relative risk of mortality 3.5 for pts with NN without CMD (95% CI: 1.1 to 11.7; p = 0.03); 2.9 for pts with NN with CMD (95% CI: 1.1 to 7.8; p = 0.03); 6.6 for pts with MN without CMD (95% CI: 2.6 to 16.5; p = 0.001); and for pts with MN with CMD.
Conclusions: Malnourished pts with CMDs have the worst survival. Malnutrition, CMDs, and rGFR are significant predictors of survival in CAPD pts.
Albumin at the Start of Peritoneal Dialysis Predicts the Development of Peritonitis in Chinese Patients
Objective: Despite the decreasing incidence of peritonitis among peritoneal dialysis (PD) patients (pts) over time, its occurrence is still associated with significant morbidity and mortality. We studied the clinical characteristics that influence the risk of dialysis-related peritonitis complications in incident Chinese pts.
Methods: Our retrospective single-center observational cohort study examined the risk factors for developing a first episode of dialysis-related peritonitis. All pts who started on PD between 1 January 2000 and 31 December 2004 at Renji Hospital, Shanghai Jiao Tong University School of Medicine, China, were included. They were followed from PD initiation to death, cessation of PD, transfer to another center, or 31 December 2006.
Results: The study recruited 240 incident continuous ambulatory PD (CAPD) pts for analysis. During the study period (626.3 patient–years), 82 first episodes of peritonitis were recorded. Low serum albumin was associated with significantly shorter peritonitis-free survival [hazard ratio (HR): 0.653; 95% confidence interval (CI): 0.447 to 0.955; p = 0.028]. The median peritonitis-free time for female subjects was worse than that for male subjects [44.1 months (range: 37.9 – 50.4 months) vs. 58.1 months (range: 50.9 – 65.4 months), p = 0.04]. Compared with nondiabetic pts, diabetic pts had a similar peritonitis-free period (p > 0.05). However, after adjustment for demographic and clinical parameters, the multivariate Cox proportional hazards model for time to first peritonitis episode showed that low serum albumin was the only independent predictor associated with peritonitis-free survival. Each increase of 10 g/L in serum albumin was associated with a 40.4% lower hazard for peritonitis (HR: 0.596; 95% CI: 0.399 to 0.891; p = 0.012). Female sex was only marginally predictive of developing peritonitis (HR: 1.571; 95% CI: 0.985 to 2.505; p = 0.058) in the multivariate model.
Conclusions: Hypoalbuminemia at the start of PD therapy is an independent predictor of subsequent peritonitis in Chinese pts. Intervention studies to reduce the peritonitis risk in this high-risk subset of pts are needed.
Effects of Inflammation, Nutrition Status, and Residual Renal Function in Peritoneal Dialysis Patients Treated with a Low-Protein Diet Combined with Keto Acids
Objective: The Dialysis Outcomes Quality Initiative guideline recommends a dietary protein intake of more than 1.2 g/kg daily to prevent protein–energy wasting in peritoneal dialysis (PD) patients. However, a low-protein diet (LPD) may preserve residual renal function (RRF) in chronic kidney disease (CKD) patients before the start of dialysis. Alpha keto acids (AKAs), which are often recommended to pre-dialysis CKD patients treated with LPD, have also been reported to be associated with both RRF and nutrition maintenance. In the present study, we conduct a randomized trial to investigate the effects of a combination of AKAs and LPD on serum cytokine levels, nutrition status, and RRF in patients performing continuous ambulatory PD (CAPD).
Methods: We randomized 89 CAPD patients into three groups, and in 78 cases, completed a 1-year follow-up with complete data. In 31 cases, patients used LPD [0.8 g/kg ideal body weight (IBW) daily] plus AKAs (LPD-AKA); in 26 cases, they used LPD (0.8 g/kg IBW daily); and in 21 cases, they use a routine diet (RPD: 1.2 g/kg IBW daily). Serum levels of albumin (Alb), prealbumin (PA), retinol-binding protein (RBP), transferrin (TRF), cholesterol (TC), triglycerides (TG), leptin, and intact parathyroid hormone were determined, and triceps skinfold thickness (TSF), mid-arm muscle circumference (MAMC), and body mass index (BMI) were measured. Changes in serum interleukin-1α (IL-1α), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and C-reactive protein (CRP) were also detected. Examinations of RRF, peritoneal ultrafiltration, residual urine volume, and fluid status were performed.
Results: Serum PA, RBP, and TRF were significantly higher both in the LPD-AKA and RPD groups (p < 0.01) than in the LPD group; however, differences in the levels of PA, RBP, and TRF between the LPD-AKA group and the RPD group were nonsignificant (NS). A NS trend toward higher Alb, TC, TG, BMI, TSF, and MAMC was also observed. Plasma levels of IL-1α, IL-6, and TNFα were lower in the LPD-AKA group than in the RPD group, but the differences were NS. Plasma levels of CRP were lower in the LPD-AKA group than in the RDP group (p < 0.01). In the LDP-AKA group, RRF remained stable, but it declined in the LPD (p < 0.05) and RPD (p < 0.05) groups.
Conclusions: A diet containing 0.8 g protein per kilogram IBW daily is safe and, when combined with AKAs, is associated with improved preservation of RRF in CAPD patients without significant malnutrition or inflammation.
The Role of Uncoupling Protein 2 Exon 8 Insertion/Deletion Polymorphism in Metabolic Disorder in Peritoneal Dialysis Patients
Objective: This cross-sectional and longitudinal cohort study investigated the impact of the uncoupling protein 2 (UCP2) exon 8 insertion/deletion (ins/del) gene polymorphism on metabolic disorder in prevalent (P) and incident (I) Chinese peritoneal dialysis (PD) patients (pts).
Methods: The study enrolled 70 P and 50 I PD pts, who then underwent genotyping of the UCP2 ins/del polymorphism. Homeostatic model assessment of insulin resistance (HOMA-IR), plasma lipid profile, C-reactive protein (CRP), ferritin, anthropometry, peritoneal glucose absorption (PGA), and the adipocytokines leptin, adiponectin, and resistin (by ABC-ELISA) were examined in the P pts, and before and after (at 3 and 6 months) initiation of PD therapy in the I pts.
Results: In the P pts, 52 had the DD genotype, and 18, the DI/II genotype. No significant differences were observed in age, sex, duration of PD, prevalence of diabetes, and PGA between these two groups. Serum leptin (1.8400 vs. 1.5950, p < 0.01) and HOMA-IR (3.7893 vs. 2.0902, p < 0.01) were significantly higher in the DD group. No significant differences in plasma lipid profile and adiponectin were observed for the two groups. Among the P pts, 49 were nondiabetic. Based on the median IR (2.5756), pts were divided into high-IR (IR ≥ 2.5756) and low-IR (IR < 2.5756) groups. The proportion of DD pts was significantly higher in the high-IR group than in the low-IR group (88.0% vs. 52.2%, p < 0.01). In 41 I pts with the DD genotype who completed the 6-month follow-up, significant increases in BMI (p < 0.05), IR (p < 0.01), serum TG (p < 0.01), and leptin (p < 0.05) were observed. The DD genotype I pts also demonstrated a significant decline in serum adiponectin (p < 0.05). No remarkable change was observed in metabolic parameters in the 9 I pts with the DI/II genotype. In the DD group, IR was positively associated with TG (r = 0.316, p < 0.01), CRP (r = 0.262, p < 0.01), ferritin (r = 0.228, p < 0.05), serum leptin (r = 0.373, p < 0.01), and PGA (r = 0.291, p < 0.05) and negatively associated with serum adiponectin (r = –0.226, p < 0.05). IR was significantly associated with serum leptin [p < 0.01; OD: 3.765; 95% confidence interval (CI): 1.664 to 8.515] and TG (p < 0.01; OD: 3.161; 95% CI: 1.483 to 6.737). TG was positively associated with serum leptin (r = 0.216, p < 0.01) and negatively associated with serum adiponectin (r = –0.214, p < 0.01). No correlations were found in the DI/II group.
Conclusions: Pts with the UCP2 DD genotype demonstrated a significant critical metabolic disorder in PD, suggesting a possible role of the UCP2 exon 8 ins/del polymorphism in metabolic disturbance under a high glucose environment.
Mo Y.,
Patterns of Incretin Secretion in End-Stage Renal Disease (ESRD) Patients Commencing Peritoneal Dialysis: Insights into Robust Traces of Diabetes Mellitus in ESRD
Background: Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) worldwide. Insulin resistance and defects in β–cell insulin secretion have long been discussed as a pathophysiologic hallmark of type 2 diabetes mellitus (DM). More recently, investigators have reported that impairment in the secretion levels or activity of key incretin hormones may also play a significant role in the development and progression of type 2 DM. Better understanding of the major incretin hormones, GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide 1), has led to important therapeutic advances in type 2 DM.
Objective: Patterns of incretin secretion have not previously been evaluated in ESRD patients (pts) commencing peritoneal dialysis (PD). The present study aimed to elucidate the clinical significance of impaired patterns of incretin secretion in DM as compared with non-DM ESRD pts commencing PD.
Method: The study enrolled 30 pts [mean age: 57.7 ± 15.1 years; 15 men (50%)] during July 2008 and February 2009. All underwent a 75-g oral glucose tolerance test (OGTT): plasma glucose, insulin, total GIP, and active GLP-1 were measured every 30 minutes for 2 hours. We compared total GIP, active GLP-1, insulin, glucose, and glucagon between DM+PD (n = 23, 76.7%) and non-DM+PD (n = 7) ESRD pts. We then compared the clinical, biochemical, and incretin secretion data between the two groups.
Results: In the DM+PD group, GIP0 was 143.1 pg/mL; GIP30, 298.1 pg/mL; GIP60, 324.7 pg/mL; GIP90, 346.7 pg/mL; and GIP120, 301.7 pg/mL; active GLP-10 was 17.5 pmol/L; GLP-130, 27.5 pmol/L; GLP-160, 36.8 pmol/L; GLP-190, 33.4 pmol/L; and GLP-1120, 27.9 pmol/L. During the 75-g OGTT, these pts showed a blunted total GIP, active GLP-1, and insulin secretion pattern as compared with the non-DM+PD pts and with a DM group with no chronic kidney disease (CKD).
Conclusions: The disturbed secretion patterns of total GIP and active GLP-1 in DM ESRD pts commencing PD may explain the change of insulin resistance in these pts. Large-scale long-term studies are needed to confirm the clinical significance of incretin and to elucidate the multipotential aspects of incretin hormones according to CKD stage and dialysis modality.