“NEPP” Peritoneal Dialysis Regimen Has Beneficial Effects on Plasma CEL and 3-DG,But Not Pentosidine,CML, and MGO

♦ Background: Standard peritoneal dialysis (PD) solutions contain high levels of glucose and glucose degradation products (GDPs), both contributing to the formation of advanced glycation end products (AGEs). We studied the contribution to plasma GDP and AGE levels of 2 PD regimens that differ in glucose and GDP loads: high load [standard PD (sPD) using 4 glucose–lactate exchanges] and low load [1 amino acid exchange, 1 icodextrin exchange, and 2 glucose–bicarbonate/lactate exchanges (“NEPP”)].♦ Methods: In a prospective crossover study (2 periods of 24 weeks), new continuous ambulatory PD patients were randomized to NEPP–sPD (n = 23) or to sPD–NEPP (n = 27).♦ Results: After the start of PD, absolute increases were observed in plasma levels of 3-deoxyglucosone (3-DG, 220.4 nmol/L, p < 0.0001) and in N_ε-(carboxymethyl) lysine (CML) in plasma proteins (0.02 μmol/L CML per 1 mol/L lysine, p < 0.0001). During the first 6 weeks, 3-DG tended to increase more with sPD treatment (p = 0.08), and CML, with NEPP treatment (p = 0.002). In both groups, N_ε-(carboxyethyl)lysine (CEL) in plasma proteins declined significantly with the start of PD. Treatment with NEPP resulted in higher levels of methylglyoxal (MGO) and lower levels of 3-DG and CEL. Pentosidine in the albumin fraction tended to increase less during NEPP treatment.♦ Conclusions: A low glucose and GDP PD regimen (NEPP) resulted in plasma levels of 3-DG and CEL that were lower than those with a glucose-based sPD regimen. Starting PD with NEPP was associated with a steeper increase in CML, and continuing treatment with NEPP resulted in higher MGO levels.     

Cost Analysis of Hemodialysis and Peritoneal Dialysis Access in Incident Dialysis Patients

♦ Background: Although several studies have demonstrated the economic advantages of peritoneal dialysis (PD) over hemodialysis (HD), few reports in the literature have compared the costs of HD and PD access. The aim of the present study was to compare the resources required to establish and maintain the dialysis access in patients who initiated HD with a tunneled cuffed catheter (TCC) or an arteriovenous fistula (AVF) and in patients who initiated PD.♦ Methods: We retrospectively analyzed the 152 chronic kidney disease patients who consecutively initiated dialysis treatment at our institution in 2008 (HD-AVF, n = 65; HD-CVC, n = 45; PD, n = 42). Detailed clinical and demographic information and data on access type were collected for all patients. A comprehensive measure of total dialysis access costs, including surgery, radiology, hospitalization for access complications, physician costs, and transportation costs was obtained at year 1 using an intention-to-treat approach. All resources used were valued using 2010 prices, and costs are reported in 2010 euros.♦ Results: Compared with the HD-AVF and HD-TCC modalities, PD was associated with a significantly lower risk of access-related interventions (adjusted rate ratios: 1.572 and 1.433 respectively; 95% confidence intervals: 1.253 to 1.891 and 1.069 to 1.797). The mean dialysis access-related costs per patient-year at risk were €1171.6 [median: €608.8; interquartile range (IQR): €563.1 - €936.7] for PD, €1555.2 (median: €783.9; IQR: €371.4 - €1571.7) for HD-AVF, and €4208.2 (median: €1252.4; IQR: €947.9 - €2983.5) for HD-TCC (p < 0.001). In multivariate analysis, total dialysis access costs were significantly higher for the HD-TCC modality than for either PD or HD-AVF (β = -0.53; 95% CI: -1.03 to -0.02; and β = -0.50; 95% CI: -0.96 to -0.04).♦ Conclusions: Compared with patients initiating HD, those initiating PD required fewer resources to establish and maintain a dialysis access during the first year of treatment.     

Peritoneal Morphology After Long-Term Peritoneal Dialysis with Biocompatible Fluid: Recent Clinical Practice in Japan

♦ Background: Morphology changes of the peritoneal membrane after long-term peritoneal dialysis (PD) consist of denudation of peritoneal mesothelial cells, interstitial sclerosis, and hyalinizing vasculopathy. Those changes are considered to be the result of uremia and bioincompatible effects of conventional acidic lactate-buffered dialysate with glucose degradation products (GDPs). In the last decade, biocompatible dialysate with neutral pH and low GDPs has become widely used. Clinical practice has been modified in Japan, especially for anuric patients, and now includes the use of hybrid therapy. The impact on peritoneal morphology has not been well reported.♦ Objective: The aim of the present study was to investigate the long-term effect on peritoneal morphology and function of biocompatible fluid use and current clinical practice in Japan, including hybrid dialysis therapy.♦ Methods: We evaluated peritoneal biopsy specimens from patients who had undergone PD for more than 3 years. We used the average peritoneal thickness (APT) of the submesothelial compact zone as a marker of interstitial sclerosis and the lumen/vessel diameter ratio (L/V ratio) at postcapillary venules as a marker of hyalinizing vasculopathy. Demography and other data for the patients, including dialysate-to-plasma (D/P) ratio of creatinine, were obtained at baseline and every 6 months by peritoneal equilibration test.♦ Results: Between 2002 and 2009, 110 patients started PD therapy with biocompatible dialysate at Tokyo University Hospital. Among them, 11 patients (8 men, 3 women; age: 54.2 ± 11.8 years; 1 with diabetes mellitus) were enrolled into this morphology study. The mean duration of PD in this group was 61 ± 11.3 months, and the mean time to peritoneal biopsy was 58 ± 15.1 months. The median APT was 180 μm (96 – 1424 μm), and the median L/V ratio was 0.66 (0.46 – 0.74). No obvious correlations between APT, L/V ratio, and PD duration were detected. The D/P creatinine of the 11 patients was maintained at a favorably low value, comparable with that of the other 99 patients.♦ Conclusions: Peritoneal dialysis therapy using biocompatible dialysate in conjunction with modification of clinical practice may minimize the progression of peritoneal interstitial sclerosis and hyalinizing vasculopathy, preserving favorable peritoneal function for more than 3 years.     

Time Course of Peritoneal Function in Automated and Continuous Peritoneal Dialysis

♦ Background and Objectives: In automated peritoneal dialysis (APD), a patient’s peritoneal membrane is more intensively exposed to fresh dialysate than it is in continuous ambulatory peritoneal dialysis (CAPD). Our aim was to study, in incident peritoneal dialysis (PD) patients, the influence of APD—compared with that of CAPD—on peritoneal transport over 4 years.♦ Design, Setting, Participants, and Measurements: Patients were included if at least 2 annual standard permeability analyses (SPAs) performed with 3.86% glucose were available while the patient was using the same modality with which they had started PD (APD or CAPD). Patients were followed until their first modality switch. Differences in the pattern of SPA outcomes over time were tested using repeated-measures models adjusted for age, sex, comorbidity, primary kidney disease, and year of PD start.♦ Results: The 59 CAPD patients enrolled were older than the 47 APD patients enrolled (mean age: 58 ± 14 years vs 49 ± 14 years; p < 0.01), and they had started PD earlier (mean start year: 2000 vs 2002). Over time, no differences in solute (p > 0.19) or fluid transport (p > 0.13) were observed. Similarly, free water transport (p = 0.43) and small-pore transport (p = 0.31) were not different between the modalities. Over time, patients on APD showed a faster decline in effective lymphatic absorption rate (ELAR: p = 0.02) and in transcapillary ultrafiltration (TCUF: p = 0.07, adjusted p = 0.05). Further adjustment did not change the results.♦ Conclusions: Compared with patients starting on CAPD, those starting on APD experienced a faster decline in ELAR and TCUF. Other transport parameters were not different over time between the groups.     

Glucose-Based Peritoneal Dialysis Solution Suppresses Adiponectin Synthesis Through Oxidative Stress in an Experimental Model of Peritoneal Dialysis

♦ Objective: Accumulation of visceral fat is one of the major risk factors for the development of cardiovascular disease in peritoneal dialysis (PD) patients. Adiponectin, an adipokine commonly regarded as a negative indicator of metabolic disease, is reported to be downregulated in its gene level in end-stage renal disease patients. Since excessive fat deposit is involved in increased reactive oxygen species (ROS), PD solution (PDS) may contribute to ROS production, resulting in dysregulation of adiponectin. In this study, we tested our hypothesis that oxidative stress induced by PDS may play a role in the regulation of adiponectin.♦ Methods: Commercial PDS containing 3.86% glucose (20 – 30 mL) was administered to SD rats for 12 weeks with and without N-acetylcysteine (NAC; 10 mmol/L). ELISA was used to quantify adiponectin in plasma and spent dialysate. For in vitro studies, fully differentiated 3T3-L1 adipocytes and adipocytes isolated from abdominal fat were treated with a high glucose solution, PDS, and H₂O₂. Adiponectin levels in the conditioned media were measured by ELISA and immunoblot assays. The mRNA levels of adiponectin in mature adipocytes were examined using real-time RT-PCR.♦ Results: The levels of adiponectin in plasma and spent dialysate were significantly downregulated by PDS and this effect was suppressed by NAC. In 3T3-L1 adipocytes, adiponectin secretion was inhibited by 50 mmol/L glucose, PDS diluted 2-fold, and H₂O₂ (200 μmol/L). In addition, H₂O₂ downregulated expression of adiponectin mRNA and secretion of adiponectin oligomer complexes.♦ Conclusions: Our data suggest that ROS induced by conventional glucose-based PDS may contribute to pathophysiological changes in abdominal fat and downregulate adiponectin secreted from adipocytes during long-term PD.     

Comparison of Direct Medical Costs Between Automated and Continuous Ambulatory Peritoneal Dialysis

♦ Objective: We set out to estimate the direct medical costs (DMCs) of peritoneal dialysis (PD) and to compare the DMCs for continuous ambulatory PD (CAPD) and automated PD (APD). In addition, DMCs according to age, sex, and the presence of peritonitis were evaluated.♦ Methods: Our retrospective cohort analysis considered patients initiating PD, calculating 2008 costs and, for comparison, updating the results for 2010. The analysis took the perspective of the Mexican Institute of Social Security, including outpatient clinic and emergency room visits, dialysis procedures, medications, laboratory tests, hospitalizations, and surgeries.♦ Results: No baseline differences were observed for the 41 patients evaluated (22 on CAPD, 19 on APD). Median annual DMCs per patient on PD were US$15 072 in 2008 and US$16 452 in 2010. When analyzing percentage distribution, no differences were found in the DMCs for the modality groups. In both APD and CAPD, the main costs pertained to the dialysis procedure (CAPD 41%, APD 47%) and hospitalizations (CAPD 37%, APD 32%). Dialysis procedures cost significantly more (p = 0.001) in APD (US$7 084) than in CAPD (US$6 071), but total costs (APD US$15 389 vs CAPD US$14 798) and other resources were not different. The presence of peritonitis increased the total costs (US$16 075 vs US$14 705 for patients without peritonitis, p = 0.05), but in the generalized linear model analysis, DMCs were not predicted by age, sex, dialysis modality, or peritonitis. A similar picture was observed for costs extrapolated to 2010, with a 10% - 20% increase for each component—except for laboratory tests, which increased 52%, and dialysis procedures, which decreased 3%, from 2008.♦ Conclusions: The annual DMCs per patient on PD in this study were US$15 072 in 2008 and US$16 452 in 2010. Total DMCs for dialysis procedures were higher in APD than in CAPD, but the difference was not statistically significant. In both APD and CAPD, 90% of costs were attributable to the dialysis procedure, hospitalizations, and medications. In a multivariate analysis, no independent variable significantly predicted a higher DMC.     

MgCaCO3 Versus CaCO3 in Peritoneal Dialysis Patients – A Cross-Over Pilot Trial

♦ Background: Despite adverse effects such as constipation, vascular calcification, and hypercalcemia, calcium-based salts are relatively affordable and effective phosphate binders that remain in widespread use in the dialysis population. We conducted a pilot study examining whether the use of a combined magnesium/calcium-based binder was as effective as calcium carbonate at lowering serum phosphate levels in peritoneal dialysis (PD) patients.♦ Methods: This was a cross-over, investigator-masked pilot study in which prevalent PD patients received calcium carbonate alone (200 mg calcium per tablet) or calcium magnesium carbonate (100 mg calcium, 85 mg magnesium per tablet). Primary outcome was serum phosphate level at 3 months. Analysis was as per protocol.♦ Results: Twenty patients were recruited, 17 completed the study. Mean starting dose was 11.35 ± 7.04 pills per day of MgCaCO₃ and 9.00 ± 4.97 pills per day of CaCO₃. Mean phosphate levels fell from 2.13 mmol/L to 2.01 mmol/L (95% confidence interval (CI): 1.76 – 2.30, p = 0.361) in the MgCaCO₃ group, and 1.81 mmol/L (95% CI: 1.56 – 2.0, p = 0.026) in the CaCO₃ alone group. Six (35%) patients taking MgCaCO₃ and 9 (54%) taking CaCO₃ alone achieved Kidney Disease Outcomes Quality Initiative (KDOQI) serum phosphate targets at 3 months. Diarrhea developed in 9 patients taking MgCaCO₃ and 3 taking CaCO₃. Serum magnesium exceeded 1.4 mmol/L in 5 patients taking MgCaCO₃ while serum calcium exceeded 2.65 mmol/L in 3 patients receiving CaCO₃. When compared to the initial dose, the prescribed dose at 3 months was reduced by 44% (to 6.41 tablets/day) in the MgCaCO₃ group and by 8% (to 8.24 pills per day) in the CaCO₃ alone group.♦ Conclusion: Compared with CaCO₃ alone, the preparation and dose of MgCaCO₃ used in this pilot study was no better at lowering serum phosphate levels in PD patients, and was associated with more dose-limiting side effects.     

Clinical Outcome of Home Hemodialysis in Patients with Previous Peritoneal Dialysis Exposure: Evaluation of the Integrated Home Dialysis Model

♦ Background:

Home dialysis is a cost-effective modality of renal replacement therapy associated with excellent outcomes. Peritoneal dialysis (PD) is the most common home-based modality, but technique failure remains a problem. Transfer from PD to home hemodialysis (HHD) allows the patient to continue with a home-based modality, but the outcomes of patients transitioning to HHD after PD are largely unknown.

♦ Methods:

In a retrospective cohort study, including all consecutive HHD patients between January 1996 and December 2011, we evaluated the outcomes of patients with previous PD exposure compared to those without. The primary outcome was the cumulative patient and technique survival. Secondary outcomes included time to first hospitalization and hospitalization rate. Data were compared using the log-rank test and a multivariable Cox proportional hazards model.

♦ Results:

Among our cohort of 207 consecutive HHD patients, 35 (17%) had previous exposure to PD. Median renal replacement therapy (RRT) vintage (12.3 years, interquartile range (IQR) 8.5 – 18.9 vs 0.9 years, IQR 0.2 – 7.5, p < 0.001) and Charlson comorbidity index (CCI) (4, IQR 2 – 6 vs 3, IQR 2 – 4, p = 0.044) were higher among patients with PD exposure than those without. Despite the difference in vintage, cumulative patient and technique survival was similar in the two groups, in both unadjusted (log-rank p = 0.893) and Cox adjusted models (hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.51 – 2.59) for patients with PD exposure compared to those without. The time to first hospitalization was shorter in patients with previous PD exposure compared to PD-naïve patients (log-rank p = 0.021). This association was preserved in the Cox proportional model (HR 1.65, 95% CI 1.08 – 2.54).

♦ Conclusion:

Despite a higher burden of comorbidity, patients with previous PD exposure had similar cumulative patient and technique survival on HHD compared to those without PD exposure. Whenever possible, HHD should be considered in PD patients in need of a new dialysis modality.     

Peritoneal Resting with Heparinized Lavage Reverses Peritoneal Type I Membrane Failure. A Comparative Study of the Resting Effects on Normal Membranes

♦ Background: Ultrafiltration failure (UFF) is a serious complication of long-term peritoneal dialysis (PD). Peritoneal rest (PR) has been demonstrated as a valid treatment to reverse the functional changes that occur in UFF. The effects of PR on a normally functioning human peritoneum are unknown but are expected to be neutral. Our hypothesis was that PR positively modifies peritoneal function in patients with UFF, in contrast to the absence of effects when PR is applied under normal conditions.♦ Patients and Methods: We studied 84 PR periods, comparing 35 patients with UFF and 49 controls (resting for abdominal surgery with temporary discontinuation of PD). We analyzed peritoneal transport pre-PR and post-PR by calculating the mass transfer coefficients of creatinine (Cr-MTAC), the dialysate/plasma creatinine ratio (D/P Cr) and the ultrafiltration (UF).♦ Results: Baseline data was similar for the 2 groups, although the UFF group had a longer median time in PD (39 [18 - 60] vs 10 [5 - 23] months; p = 0.00001). Peritoneal rest induced a decrease in D/P Cr, Cr-MTAC and an increase in UF capacity in the UFF group (p = 0.0001, p = 0.004 and p = 0.001, respectively), without causing changes in the control group. Peritoneal rest in patients with more than 6 months of UFF was not able to reduce peritoneal solute transport or improve UF capacity. Response to PR did not differ among UFF patients with or without a previous history of peritonitis. Peritoneal rest enabled patients with UFF to continue on PD for a median time of 23 months (range, 13 - 46 months).♦ Conclusions: Peritoneal rest induces functional changes in patients with UFF but not in those with no functional abnormalities. This demonstrates that PR works only when abnormal but reversible functional conditions are present. However, the effect is highly dependent on how early PR is applied.     

Bioimpedance Spectroscopy for the Detection of Fluid Overload in Chinese Peritoneal Dialysis Patients

♦ Background: Fluid overload probably contributes to the cardiovascular risk of peritoneal dialysis (PD) patients. We studied the relationship between over-hydration as determined by bioimpedance spectroscopy and dialysis adequacy, nutritional status, and arterial stiffness in Chinese PD patients.♦ Methods: We studied 122 asymptomatic prevalent PD patients: bioimpedance spectroscopy, arterial pulse wave velocity, dialysis adequacy and nutritional status were determined.♦ Results: Of the 122 patients, 88 (72.1%) had over-hydration of ≥ 1 L, while 25 (20.5%) were ≥ 5 L. Over-hydration significantly correlated with total body water (r = 0.474, p < 0.001) and extracellular water (r = 0.755, p < 0.001). Over-hydration was more severe in male and diabetic patients, and significantly correlated with Charlson’s comorbidity score, blood pressure, body mass index, body weight, peritoneal transport characteristics, and carotid-femoral pulse wave velocity. Over-hydration significantly correlated with Kt/V (r = -0.287, p = 0.016), serum albumin level (r = -0.465, p < 0.001) and malnutrition inflammation score (r = 0.410, p = 0.006), but not residual renal function.♦ Conclusion: Over-hydration is common in asymptomatic Chinese PD patients. The degree of over-hydration is particularly pronounced in patients who are inadequately dialyzed, have multiple comorbid conditions and low serum albumin levels. Over-hydration is associated with high blood pressure and arterial stiffness, and may contribute to the excessive risk of cardiovascular disease in this group of patients.     

Impact of metformin use on the prognostic value of lactate in sepsis

Objective

The objective of this study is to determine if metformin use affects the prevalence and prognostic value of hyperlactatemia to predict mortality in septic adult emergency department (ED) patients.

Methods

This is a single-center retrospective cohort study. Emergency department providers identified study subjects; data were collected from the medical record.

Patients

Adult ED patients with suspected infection and 2 or more systemic inflammatory response syndrome criteria were included. The outcome was 28-day mortality. The primary risk variable was serum lactate (<2.0, 2.0-3.9, ≥4.0 mmol/L) categorized by metformin use; covariates: demographics, Predisposition, Infection, Response, Organ Dysfunction score and metformin use contraindications.

Setting

The study was conducted at an urban teaching hospital; February 1, 2007 to October 31, 2008.

Results

A total of 1947 ED patients were enrolled; 192 (10%) were taking metformin; 305 (16%) died within 28 days. Metformin users had higher median lactate levels than nonusers (2.2 mmol/L [interquartile range, 1.6-3.2] vs 1.9 mmol/L [interquartile range, 1.3-2.8]) and a higher, although nonsignificant, prevalence of hyperlactatemia (lactate ≥4.0 mmol/L) (17% vs 13%) (P = .17). In multivariate analysis (reference group nonmetformin users, lactate <2.0 mmol/L), hyperlactatemia was associated with an increased adjusted 28-day mortality risk among nonmetformin users (odds ratio [OR], 3.18; P < .01) but not among metformin users (OR, 0.54; P = .33). In addition, nonmetformin users had a higher adjusted mortality risk than metformin users (OR, 2.49; P < .01). These differences remained significant when only diabetic patients were analyzed.

Conclusions

In this study of adult ED patients with suspected sepsis, metformin users had slightly higher median lactate levels and prevalence of hyperlactatemia. However, hyperlactatemia did not predict an increased mortality risk in patients taking metformin.     

Body Mass Index and Mortality Risk in Asian Peritoneal Dialysis Patients in Hong Kong—Impact of Diabetes and Cardiovascular Disease Status

♦ Background: Obesity increases mortality in the general population, but improves survival in hemodialysis patients. In peritoneal dialysis (PD) patients, the reported effect is controversial. We investigated the effect of body mass index (BMI) on patient survival in Asian PD patients.♦ Methods: The survival of incident Asian PD patients from 2001 to 2008 in a single center in Hong Kong was analyzed retrospectively. Baseline demographic and clinical data were collected from patient records. Patients who had a total Kt/V below 1.7 or who died within 6 months were excluded. The BMI was categorized using the World Health Organization recommendation for Asian populations.♦ Results: In the 274 study patients [154 men (56%); 138 with diabetes (50.4%); mean age: 63.4 ± 14.6 years; mean BMI: 21.97 ± 3.23 kg/m²; 37 underweight (13.5%); 35 obese (12.8%)], the relative risk (RR) for mortality [adjusted for age, diabetes status, and cardiovascular disease (CVD)] was similar for the normal and overweight groups, but higher for the underweight (RR: 1.909; p = 0.028) and obese groups (RR: 1.799; p = 0.048). The increased mortality in obese patients was more prominent in patients with diabetes (RR: 1.9 vs 1.19 in patients without diabetes; p = 0.074 and 0.76 respectively), and in patients with CVD (RR: 8.895 vs 1.642 in patients without CVD; p = 0.012 and 0.122 respectively).♦ Conclusions: In Asian PD patients, the relationship between BMI and mortality was U-shaped, with higher mortality in the underweight and obese patients. The negative impact of obesity was more prominent in patients with diabetes and CVD.     

Comparative Mortality-Predictability Using Alkaline Phosphatase and Parathyroid Hormone in Patients on Peritoneal Dialysis and Hemodialysis

♦ Background: In hemodialysis (HD) patients, serum alkaline phosphatase (ALP) and parathyroid hormone (PTH) derangements are associated with mortality, but outcome-predictability using ALP and PTH in peritoneal dialysis (PD) patients remains uncertain.♦ Methods: In a cohort of 9244 adult PD patients from a large national dialysis organization (entry period 2001 - 2006, with follow-up through 2009), we used multivariable Cox models adjusted for case-mix and laboratory covariates to examine the associations of time-averaged ALP and PTH with all-cause mortality. We then compared mortality-predictability using ALP and PTH in 9244 PD and 99 323 HD patients.♦ Results: In PD patients, ALP concentrations exceeding 150 U/L were associated with increased mortality (reference ALP: 70 to <90 U/L). Hazard ratios (HRs) and 95% confidence intervals (CIs) were 1.18 (1.03 to 1.36), 1.27 (1.08 to 1.50), 1.49 (1.23 to 1.79), and 1.35 (1.19 to 1.53) for ALP concentrations of 150 to <170 U/L, 170 to <190 U/L, 190 to <210 U/L, and ≥210 U/L respectively. In contrast, we observed a U-shaped association between PTH concentration and death risk in PD patients, with PTH concentrations of less than 200 pg/mL and 700 pg/mL or more associated with increased mortality (reference PTH: 200 to <300 pg/mL). Hazard ratios and 95% CIs were 1.25 (1.12 to 1.41), 1.12 (1.02 to 1.23), 1.06 (0.96 to 1.18), 1.09 (0.97 to 1.24), 1.12 (0.97 to 1.29), 1.18 (0.99 to 1.40), and 1.23 (1.09 to 1.38) for PTH concentrations of <100 pg/mL, 100 to <200 pg/mL, 300 to <400 pg/mL, 400 to <500 pg/mL, 500 to <600 pg/mL, 600 to <700 pg/mL, and ≥700 pg/mL respectively. Compared with PD patients having serum concentrations of ALP and PTH within reference ranges, patients on HD experienced increased mortality across all ALP and PTH concentrations, particularly those in the lowest and highest categories.♦ Conclusions: In summary, higher ALP concentrations are associated with increased mortality, and lower and higher PTH concentrations are both associated with death risk in PD patients. The utility of ALP in the management of chronic kidney disease mineral bone disorders in PD patients warrants further study.     

Neutrophil Gelatinase-Associated Lipocalin in Peritoneal Effluent: Evaluation in Peritoneal Dialysis Patients in Basal Condition

♦ Purpose: In the present study, we assessed expression of neutrophil gelatinase-associated lipocalin (NGAL) in peritoneal effluent (pNGAL) from peritoneal dialysis (PD) patients, and we evaluated factors that might affect its level in basal conditions.♦ Methods: Our cross-sectional study included all 69 patients on PD at our institution. We evaluated patient history, hydration status, residual renal function, indices of dialysis adequacy, peritoneal transport type, serum C-reactive protein, ferritin, serum NGAL (sNGAL) and pNGAL. Univariate and multivariate linear regression models were used to evaluate predictors of pNGAL.♦ Results: Of the study patients, 39 (56.5%) were men, and 54 (78.3%) were on continuous ambulatory PD. Median age in the group was 61 years [interquartile range (IQR): 46.5 - 71 years]. Median sNGAL was 487 ng/mL (IQR: 407 - 586 ng/mL), and median pNGAL was 35 ng/mL (IQR: 21 - 46 ng/mL). dNGAL correlated directly with weekly dialytic clearance of creatinine (ρ = 0.291, p = 0.02) and with sNGAL (ρ = 0.269, p = 0.031). The same variables were also independent predictors of pNGAL (β = 0.30 and 0.29 respectively, both p < 0.05) in multivariate analysis.♦ Conclusions: In our analysis, basal levels of pNGAL were influenced by sNGAL and by dialytic clearance of creatinine.Key words: NGAL, biomarkers, peritoneal effluentNeutrophil gelatinase-associated lipocalin (NGAL) is a granulocyte-secreted polypeptide that specifically blocks bacterial growth by interfering with bacterial siderophores (1). Its role as marker has been evaluated in several conditions, including acute and chronic kidney disease (CKD), infections, and cancers. Moreover, some studies showed that NGAL secretion can be induced in epithelial cells during inflammatory insult. Specifically, Leung and colleagues (2) demonstrated secretion of NGAL by peritoneal mesothelial cells in a small group of peritoneal dialysis (PD) patients and suggested the usefulness of NGAL in PD effluent (pNGAL) for the diagnosis of peritonitis.Conversely, serum NGAL (sNGAL) is known to be high in patients with CKD (3), and high sNGAL might be paralleled by high pNGAL in PD patients. Moreover, certain systemic conditions such as hydration status or systemic inflammation may affect sNGAL (4) and consequently pNGAL. To date, no study assessing the possible interference of PD modality and systemic conditions on pNGAL concentration has been reported.The aim of the present study was to evaluate the consistency of pNGAL in basal conditions for describing a peritoneal local process and to evaluate how PD and systemic conditions might affect pNGAL values.     

Baseline FGF23 is Associated with Cardiovascular Outcome in Incident PD Patients

♦ Background:

Fibroblast growth factor 23 (FGF23) is a phosphate regulating protein. Several studies demonstrated that elevated FGF23 is independently associated with mortality for early-stage chronic kidney disease and incident hemodialysis (HD) patients. However, little is known about the significance of elevated FGF23 in peritoneal dialysis (PD) patients. Here, we analyzed the association of FGF23 with cardiovascular (CV) events, all-cause mortality, residual renal function (RRF), and CV parameters in PD patients.

♦ Methods:

The present study is a single-center, retrospective study. Patients who started PD at Seoul National University Hospital between January 2005 and July 2011 and whose baseline serum samples were available were enrolled. C-terminal FGF23 was measured. Subjects were divided into 2 groups; lower 2 tertiles (FGF23 ≤ 119.0 RU/mL) and top tertile (FGF23 > 119.0 RU/mL). The primary outcome was time to fatal or non-fatal CV events. In the subgroup analysis, the associations of FGF23 with aortic stiffness or with vascular calcification were analyzed.

♦ Results:

A total of 205 incident PD patients were analyzed. Mean duration of follow-up was 41.6 ± 20.0 months. The baseline median FGF23 level was 78.6 RU/mL (inter-quartile range [IQR], 34.1 – 155.0). At baseline, subjects in the higher FGF23 group were younger, and had a lower RRF, lower prevalence of diabetes mellitus (DM), and cerebrovascular disease. During follow-up, 22 of the 205 patients (10.7%) reached primary outcome. After adjustment for age, DM, pre-existing coronary artery disease, cerebrovascular disease, congestive heart failure, and left ventricular mass index, the higher FGF23 group exhibited significantly higher risk of primary outcome, compared with the lower group (hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.05 – 6.12; p = 0.045). There were no significant differences in all-cause mortality and development of anuria between the 2 FGF23 groups. In the subgroup analysis, FGF23 groups were not associated with pulse wave velocity and abdominal aortic calcification score.

♦ Conclusion:

Elevated FGF23 is associated with higher risk of adverse CV outcome for incident PD patients.     

Occult metformin toxicity in three patients with profound lactic acidosis

There are 20.8 million Americans with diabetes, and metformin is the most commonly prescribed oral diabetes agent. A review of our metformin experience highlights common pitfalls that lead to life-threatening or fatal poisonings. We describe 3 patients with metformin toxicity; 2 of 3 patients were prescribed metformin despite end-stage renal disease (ESRD). Case 1: a 40-year-old woman presented after a polysubstance overdose. Within 8 h, vomiting and lethargy developed; a profound acidosis, pH 6.95, pCO(2) 26, pO(2) 195, and elevated serum lactate 21 mmol/L (ref 0.5-1.6 mmol/L) were noted. Further inquiry revealed that the patient had ingested metformin. She was intubated; bicarbonate therapy and hemodialysis were initiated; however, she became hypotensive and died. A metformin level was 150 μg/mL (therapeutic 1-2 μg/mL). Case 2: a 69-year-old woman with non-insulin-dependent diabetes mellitus (NIDDM) and ESRD presented to the Emergency Department (ED), having missed dialysis. She was sluggish and complained of abdominal pain; an acidosis, pH 7.37, pCO(2) 20, pO(2) 171; anion gap 38, and elevated serum lactate 18.9 mmol/L were noted. Hemodialysis was initiated when it was revealed that she took metformin daily. She improved rapidly and a metformin level was 27.4 μg/mL. Case 3: a 57-year-old woman with a history of NIDDM and ESRD presented with dyspnea. Laboratory studies showed pH 7.03, pCO(2) 21, pO(2) 99; anion gap 36, and lactate 16 mmol/L. Bicarbonate therapy and hemodialysis were initiated after discovering that she had recently been prescribed metformin. She had a fatal cardiac arrest after dialysis was completed. We describe 3 ED patients with occult metformin toxicity diagnosed after laboratory results showed an anion gap metabolic acidosis and elevated lactate levels. All patients had lethargy, vomiting, or abdominal pain, also suggesting sepsis or mesenteric infarction. Despite sodium bicarbonate therapy and hemodialysis, metformin-associated lactic acidosis was fatal in 2 of 3 patients. Emergency Physicians must be vigilant to recognize metformin toxicity in patients at high risk for metformin-associated lactic acidosis.     

Lifetime Costs for Peritoneal Dialysis and Hemodialysis in Patients in Taiwan

♦ Background: This study compared the lifetime costs for peritoneal dialysis (PD) and hemodialysis (HD) patients in Taiwan.♦ Methods: Using the National Health Insurance (NHI) database of all end-stage renal disease patients on maintenance dialysis registered from July 1997 to December 2005, we matched eligible PD patients with eligible HD patients on age, sex, and diabetes status. The matched patients were followed until 31 December 2006. Patients were excluded if they were less than 18 years of age, had been diagnosed with cancer before dialysis, or had been dialyzed at centers or clinics other than hospitals. Outcomes—including life expectancy, total lifetime costs, and costs per life-year paid by the NHI—were estimated and compared.♦ Results: The 3136 pairs of matched PD and HD patients had a mean age of 53.2 ± 15.4 years. The total lifetime cost for PD patients (US$139 360 ± US$8 336) was significantly lower than that for HD patients (US$185 235 ± US$9 623, p < 0.001). Except for patients with diabetes (who had a short life expectancy), the total lifetime cost was significantly lower for PD patients than for HD patients regardless of sex and age (p < 0.01).♦ Conclusion: In Taiwan, the total lifetime costs paid by the NHI were lower for PD than for HD patients.