Relationship between sodium removal, hydration and outcomes in peritoneal dialysis patients.

BACKGROUND: Fluid overload (FO) in peritoneal dialysis (PD) patients is associated with mortality. We explore if low daily sodium removal is an independent risk factor for mortality. We examined severely FO PD patients established for >1 year in expectation that PD prescription would have been optimized for solute clearance and ultrafiltration. We also wish to determine the relationship between kt/v and sodium removal. METHODS: Retrospective analysis of 231 PD patients with FO ≥2.0 L and compared with 218 PD patients who were euvolaemic throughout their PD treatment. Patients were followed up until death censored for transplantation. RESULTS: Mean daily sodium removal in overhydrated patients was only 75 mmoles (=1.7 g). CAPD usage was more common in patients with the highest sodium removal. Achievement of UK guidelines for solute clearance and daily fluid removal were not independent predictors of mortality. Markers of sarcopenia (low serum albumin and high CRP) were associated with increased mortality, but these parameters were not independent predictors in a model that included functional assessment (Karnofsky score). Daily sodium removal was not predictive of mortality but the imprecision of clinically used sodium assay should be noted. The correlation between Na and kt/v is statistically significant but R2 was weak at .07. CONCLUSION: While diabetic males were more likely to become overhydrated, these factors did not increase mortality further. Traditional targets of 'dialysis adequacy' did not predict survival. Kt/v is not a good indicator of sodium removal which can be surprisingly low. Measuring sodium clearance may help clinicians optimize PD modality (CAPD vs. APD).

Is overhydration in peritoneal dialysis patients associated with cardiac mortality that might be reversible?

AIM: To study the relationship between overhydration (OH) in peritoneal dialysis (PD) patients and cardiac mortality. METHODS: OH, as measured by body composition monitor (BCM), is associated with increased mortality in dialysis patients. BCM has been used to guide treatment on the assumption that correcting OH will improve cardiac morbidity and mortality although data demonstrating causality that is reversible is limited. We wished to determine if OH in PD patients predicted cardiac mortality, and if there was a correlation between OH and cardiac troponin-T (cTnT) levels. Finally, we wished to determine if improving OH values would lead to a decrement in cTnT. All prevalent PD patients over the study period of 57 mo who had contemporaneous BCM and cTnT measurements were followed irrespective of transplantation or PD technique failure. We also studied a cohort of patients with who had severe OH (> +2L). The Fresenius Body Composition Monitor was used to obtain hydration parameters. cTnT levels were done as part of routine clinical care. Data was analysed using SPSS version 20.0. RESULTS: There were 48 deaths in the 336 patients. The patients that died from cardiac or non-cardiac causes were similar with respect to their age, incidence of diabetes mellitus, gender, ethnicity and cause of renal failure. However, the patients with cardiac causes of death had significantly shorter dialysis vintage (10.3 mo vs 37.0 mo, P < 0.0001) and were significantly more overhydrated by BCM measurement (2.95 L vs 1.35 L, P < 0.05). The mean (standard error of the means) hydration status of the 336 patients was +1.15 (0.12) L and the median [interquartile range (IQR)] cTnT level was 43.5 (20-90) ng/L. The cTnT results were not normally distributed and were therefore transformed logarithmically. There was a statistically significant correlation between Log (cTnT) with the OH value (Spearman r value 0.425, P < 0.0001). We identified a sub-group of patients that were severely overhydrated; median (IQR) hydration at baseline was +2.7 (2.3 to 3.7) L. They were followed up for a minimum of 6 mo. Reduction in OH values in these patients over 6 mo correlated with lowering of cTnT levels (Spearman r value 0.29, P < 0.02). CONCLUSION: Patients that were overhydrated had higher cTnT, and had deaths that were more likely to be cardiac related. Reduction in OH correlated with lowering of cTnT.

Clinical significance of multi-frequency bioimpedance spectroscopy in peritoneal dialysis patients: independent predictor of patient survival.

BACKGROUND: It is becoming increasingly evident that the accurate assessment of hydration status is critical to care of a dialysis patient. Using the Body Composition Monitor, different parameters (overhydration (OH), extra-cellular water/total body water (ECW/TBW) or OH/ECW) have been proposed to indicate hydration status. We wished to determine which parameter (if any) was most predictive of all-cause mortality, and if this was independent of nutritional indices. METHODS: We performed a single-centre retrospective analysis of prospectively collected data of all peritoneal dialysis (PD) patients between 1 January 2008 and 30 March 2012. Record review was undertaken to establish patient survival, clinical and demographic data. Follow-up was continued even after PD technique failure (transfer to haemodialysis) and transplantation. RESULTS: The study included 529 patients. OH index (OH and OH/ECW) was the independent predictor of mortality in multi-variate analysis. ECW/TBW as a continuous variable was not associated with increased risk of death. In contrast, patients that were severely overhydrated (highest 33%) had hazard ratios (HRs) that were statistically significant irrespective of the parameter used to define hydration. Using OH, severely overhydrated patients had an HR of 1.83 [95% confidence interval (CI) 1.19-2.82, P < 0.01], OH/ECW: 2.09 (95% CI 1.36-3.20, P < 0.001) and ECW/TBW: 2.05 (95% CI 1.31-3.22, P < 0.005). CONCLUSIONS: Our results also indicated that there was no influence of body mass index (BMI) on the hydration parameter OH/ECW. OH/ECW remained an independent predictor of mortality when the BMI and lean tissue index were included in multivariate model. However, it remains to be determined if correcting the OH status of a patient will lead to improvement in mortality.

Intraperitoneal vancomycin concentrations during peritoneal dialysis-associated peritonitis: correlation with serum levels.

BACKGROUND: For the treatment of peritoneal dialysis-associated peritonitis (PDP), it has been suggested that serum concentrations of vancomycin be kept above 12 mg/L-15 mg/L. However, studies correlating vancomycin concentrations in serum and peritoneal dialysate effluent (PDE) during active infection are sparse. We undertook the present study to investigate this issue and to determine whether achieving the recommended serum level of vancomycin results in therapeutic levels intraperitoneally. METHODS: We studied patients treated with intraperitoneal (i.p.) vancomycin for non-gram-negative PDP. We gave a single dose (approximately 30 mg/kg) at presentation, and we subsequently measured vancomycin levels in PDE on day 5; we wanted to determine if efflux of vancomycin from serum to PDE during a 4-hour dwell was consistent and resulted in therapeutic levels. RESULTS: Of the 48 episodes of PDP studied, serum vancomycin concentrations exceeding 12 mg/L were achieved in 98% of patients, but in 11 patients (23%), a PDE vancomycin level below 4 mg/L--the minimal inhibitory concentration (MIC) of many gram-positive organisms--was observed at the end of a 4-hour dwell on day 5. The correlation between the concentrations of vancomycin in serum and PDE (from efflux of antibiotic over 4 hours) was statistically significant, but poor (R(2) = 0.18). CONCLUSIONS: Our data support the International Society for Peritoneal Dialysis statement that adequate serum vancomycin concentrations can be achieved with intermittent dosing (single dose every 5 days), but cannot guarantee therapeutic PDE levels in the treatment of PDP. Intermittent dosing of vancomycin may not consistently result in PDE concentrations markedly greater than MIC of many important pathogens. Although the clinical significance of this finding remains to be determined, it may be preferable to give smaller but more frequent doses of PDE vancomycin (continuous dosing) for adults with PDP (as is currently recommended for children).

Evaluation of an enzyme immunoassay for plasma-free metanephrines in the diagnosis of catecholamine-secreting tumors.

OBJECTIVE: To define the test characteristics of an enzyme immunoassay (EIA) for plasma-free metanephrines (metanephrine and normetanephrine) in the diagnosis of pheochromocytoma and paraganglioma. DESIGN: Prospective observational design from a single University Hospital. Twenty-four hour urine for catecholamines and plasma for free metanephrines were collected from patients with a clinical suspicion of pheochromocytoma or paraganglioma. Patient records were reviewed for clinical data, follow-up, imaging and laboratory results to establish or exclude the diagnosis of pheochromocytoma. PATIENTS AND METHODS: Out of 178 consecutive patients, 10 had a paraganglioma and 12 had a pheochromocytoma: 156 were finally judged not to harbour active tumors and were therefore considered as controls. The main outcome measure was the diagnosis or exclusion of paraganglioma or pheochromocytoma and test characteristics of plasma-free metanephrines measured by EIA. RESULTS: Urinary epinephrine had a sensitivity of 45.5% and norepinephrine a sensitivity of 75% (98.8% specificity) for the diagnosis of pheochromocytoma. Plasma-free metanephrine and normetanephrine both had a sensitivity of 66.7% and a specificity of 100%, but when combined (either positive) they demonstrated a 91.7% sensitivity with a preserved specificity of 100%. For the diagnosis of paraganglioma, urinary norepinephrine gave slightly better results than plasma-free metanephrines, but combined testing was of no additional value. CONCLUSIONS: Plasma-free metanephrines measured by EIA have better diagnostic test characteristics than urinary catecholamines in the diagnosis of pheochromocytoma. The EIA offers a simple and effective measurement of plasma-free metanephrines.

Pretransplantation levels of C-reactive protein predict all-cause and cardiovascular mortality, but not graft outcome, in kidney transplant recipients.

BACKGROUND: Chronic inflammation, the common pathway that leads to cardiovascular disease and chronic allograft nephropathy after transplantation, is prevalent in patients with end-stage renal failure. We set out to investigate the hypothesis that enhanced pretransplantation C-reactive protein (CRP) levels and Chlamydia seropositivity, both markers of an altered immune response, would predict graft failure and mortality in patients receiving renal replacement therapy. METHODS: A retrospective study of 115 patients, based on CRP levels in pretransplantation serum (group 1, 0 to 5 mg/L; group 2, 5 to 10 mg/L; group 3, >10 mg/L), were investigated for the following end points: transplant rejection, graft failure, and all-cause and cardiovascular mortality. RESULTS: There were no correlations between CRP levels or Chlamydia seropositivity with respect to rejection rates or graft failure. Furthermore, there was no relationship between Chlamydia seropositivity and survival. All-cause and cardiovascular mortality were significantly greater in patients with CRP levels greater than 10 mg/L and 5 to 10 mg/L compared with those with CRP levels less than 5 mg/L. All-cause mortality rates were 5% in the 0-to-5-mg/L group, 20% in the 5-to-10-mg/L group, and 44% in the greater-than-10-mg/L group. With regard to cardiovascular mortality, death rates were 0% in the 0-to-5-mg/L group, 10% in the 5-to-10-mg/L group, and 22% in the greater-than-10-mg/L group. Univariate analysis of cardiovascular mortality and covariates showed a significant relationship with age (relative risk [RR], 1.07; P < 0.05), diabetes (RR, 5.6; P < 0.05), aspirin intake (RR, 0.2; P < 0.05), antihypertensive therapy (RR, 0.02; P < 0.05), and CRP level (RR, 11; P < 0.05), but CRP level remained the only significant predictor (RR, 1.19; P < 0.05) on multivariate analysis. CONCLUSION: Pretransplantation CRP level is independently associated with all-cause and cardiovascular mortality in our cohort of transplant recipients and may be a useful predictive marker in the follow-up of posttransplantation patients.