Francesca Martino

Is brain natriuretic peptide a reliable biomarker of hydration status in all peritoneal dialysis patients

Background: Achievement of euvolemia is a fundamental challenge in the peritoneal dialysis (PD) population. Bioimpedance spectroscopy (BIS) is one of the best techniques for routine assessment of hydration status (HS) in PD, but in recent years, the role of brain natriuretic peptides (BNP) in the assessment of volume status has gained interest. The aim of this study was to investigate the relation between BNP and volume status as measured by BIS in PD patients and to assess how these variables correlate according to the time that a patient has been on PD. Methods: We prospectively studied 68 PD patients from whom measurements of BNP and assessments of HS by BIS were performed every 3 months. Three groups were defined based on HS: group A, measurements of HS <-1.1 liters (underhydrated); group B, measurements of HS between -1.1 and +1.1 liters (normohydrated), and group C, measurements of HS >+1.1 liters (overhydrated). Measurements were also separated according to the time on PD (<6 vs. ≥6 months). Correlation between HS and BNP was performed using Spearmans correlation. Results: We performed a total of 478 measurements of HS and BNP. There was a statistically significant difference in BNP (p < 0.001) among three HS groups, with higher levels of BNP detected in overhydrated patients. We found a positive correlation between HS and BNP (rs = 0.28; p <0.001) that seemed stronger in the first 6 months on PD (rs = 0.42; p = 0.006). Conclusions: BNP correlated positively with fluid overload measured by HS, and this correlation was stronger in the first 6 months on PD.

Abdominal Aortic Calcification is an Independent Predictor of Cardiovascular Events in Peritoneal Dialysis Patients

Abdominal aortic calcification (AAC) is reported as a predictor for cardiovascular events in general population and in hemodialysis patients. At present, there are no AAC data in peritoneal dialysis. The purpose of this study was to evaluate the prognostic role of AAC score on cardiovascular events in peritoneal dialysis patients. Seventy‐four peritoneal dialysis patients were enrolled. AAC was measured on baseline lateral abdomen radiographs by the semi‐quantitative method as described by Kauppila. The other cardiovascular risk factors were obtained from patient history and blood examination. The Kaplan–Meier method was used to evaluate freedom from cardiovascular events, and differences were assessed with the log‐rank statistic. Multivariate Cox regression models addressed time to cardiovascular events. The median period of follow‐up was 30.5 months (IQR 19.4–32.7). During follow‐up, there were 29 cardiovascular events (39.2%). In univariable analysis, patients age (HR = 1.050; P = 0.001), urine output (HR = 0.999; P = 0.02), and AAC stratified by tertiles (overall P‐value < 0.001) were significantly associated with cardiovascular events. In multivariable regression analysis, AAC score stratified by tertiles was the only independent predictor for cardiovascular events (overall P‐value <0.001). To our knowledge, we have shown for the first time that AAC score is an independent predictor of cardiovascular events in peritoneal dialysis patients. Risk stratification by assessment of AAC score may provide important information for the management of cardiovascular disease in peritoneal dialysis patients without any additional expense, because these patients have several abdominal X‐ray scans to evaluate the catheter position.

Bioimpedance and Brain Natriuretic Peptide in Peritoneal Dialysis Patients

Assessment of ideal body weight in peritoneal dialysis (PD) patients is important for clinical practice. Fluid overload may produce hypertension, reduced arterial distensibility, left ventricular hypertrophy. All these are risk factors for mortality in PD patients: cardio- and cerebrovascular events are the main causes of morbidity and mortality in PD population. Nowadays, a clear and widely accepted definition of ideal body weight in PD patients does not exist. Probably the ideal body weight is the weight at which the extra cellular volume is normal. Many different tools have been used to assess the hydration status in dialysis patients. Ultrasonic evaluation of inferior vena cava diameter only assesses intravascular volume, and is also influenced by diastolic dysfunction and is thus a reflection of preload and not of tissue hydration. Direct measurement of extra cellular and total body water by dilution methods is considered as the golden standard, but these techniques are laborious and expensive. Parameters, such as brain natriuretic peptide (BNP) or NT-proBNP can reflect changes in hydration status and may help the nephrologist to estimate it. Natriuretic peptides are influenced both by preload and ventricular abnormalities and in patients with renal failure accumulation can occur. Bioimpedance is an accurate, reproducible, not expensive and not invasive technique that permits a good evaluation of hydration status in PD and can drive the nephrologist in his clinical choices. Clinical evaluation, strict control of body weight, diuresis, sodium and fluids intakes, bioimpedance monitoring and serum levels of natriuretic peptides may all together help us to maintain the PD patient euvolemic.

Neutrophil Gelatinase-Associated Lipocalin in the Early Diagnosis of Peritonitis: The Case of Neutrophil Gelatinase-Associated Lipocalin

Neutrophil gelatinase-associated lipocalin (NGAL), a protein involved in iron handling, has been recognized as a marker of inflammation. In this regard, serum and urine NGAL levels have proven a useful diagnostic tool for acute kidney injury. Bacterial peritonitis is an all too common complication of peritoneal dialysis (PD) and while diagnosis in most cases is routine, there are times when patients present with typical symptoms but do not have an elevated PD effluent white blood cell count. Furthermore, patients may present with an elevated PD fluid white count, a cloudy effluent and no evidence of active infection. In these cases, a discriminating role for peritoneal fluid NGAL would be useful to distinguish bacterial and nonbacterial PD fluid infection. A small case control study was performed which demonstrated a very high sensitivity and specificity for peritoneal fluid NGAL. These preliminary data show that peritoneal fluid NGAL may be a useful tool for the early and accurate diagnosis of peritonitis.

Cost-effectiveness analysis of online hemodiafiltration versus high-flux hemodialysis.

Background Clinical studies suggest that hemodiafiltration (HDF) may lead to better clinical outcomes than high-flux hemodialysis (HF-HD), but concerns have been raised about the cost-effectiveness of HDF versus HF-HD. Aim of this study was to investigate whether clinical benefits, in terms of longer survival and better health-related quality of life, are worth the possibly higher costs of HDF compared to HF-HD. Methods The analysis comprised a simulation based on the combined results of previous published studies, with the following steps: 1) estimation of the survival function of HF-HD patients from a clinical trial and of HDF patients using the risk reduction estimated in a meta-analysis; 2) simulation of the survival of the same sample of patients as if allocated to HF-HD or HDF using three-state Markov models; and 3) application of state-specific health-related quality of life coefficients and differential costs derived from the literature. Several Monte Carlo simulations were performed, including simulations for patients with different risk profiles, for example, by age (patients aged 40, 50, and 60 years), sex, and diabetic status. Scatter plots of simulations in the cost-effectiveness plane were produced, incremental cost-effectiveness ratios were estimated, and cost-effectiveness acceptability curves were computed. Results An incremental cost-effectiveness ratio of €6,982/quality-adjusted life years (QALY) was estimated for the baseline cohort of 50-year-old male patients. Given the commonly accepted threshold of €40,000/QALY, HDF is cost-effective. The probabilistic sensitivity analysis showed that HDF is cost-effective with a probability of ~81% at a threshold of €40,000/QALY. It is fundamental to measure the outcome also in terms of quality of life. HDF is more cost-effective for younger patients. Conclusion HDF can be considered cost-effective compared to HF-HD.

Hemolytic Uremic Syndrome and Kidney Transplantation: A Case Series and Review of the Literature

Background: Hemolytic uremic syndrome (HUS) can be triggered by Shiga toxin producing Escherichia coli (STEC) infection or it can be defined as atypical HUS (aHUS) if it is related to uncontrolled complement activation. aHUS is characterized by a high incidence of recurrence after kidney transplantation, and it can also occur de novo in transplant recipients. Eculizumab is used both to prevent and to treat aHUS following kidney transplantation. In this paper, we report our centre experience and we present 4 cases of HUS in patients who underwent kidney transplantation. Methods: This is a single-center experience about HUS development in transplanted patients. Results: Patient 1 with end-stage renal disease (ESRD) due to STEC-HUS undergoing kidney transplantation without prophylactic therapy with eculizumab. Patient 2 with HUS secondary to an episode of diarrhea at 8 years old. After a slow progression to ESRD, she underwent kidney transplantation and she received prophylactic therapy with eculizumab due to the presence of anti-complement factor H antibodies. Patient 3 underwent pre-emptive living donor ABO-incompatible kidney transplantation and developed HUS secondary to antibody-mediated rejection. Patient 4 developed de novo HUS 16 years after kidney transplantation without a known cause. Conclusion: The correct diagnosis of HUS and the identification of the complement component alterations in case of aHUS are important parameters required to predict the risk of post-transplant recurrence of the disease. In the cases we reported, eculizumab has been found to be effective both to prevent and to treat aHUS following kidney transplantation.

Contents Vol. 42, 2016

121 Selected Abstracts from the 34th Vicenza Course on AKI & CRRT Vicenza, June 7–10, 2016 (available online only)

THE ROLE OF NGAL IN PERITONEAL DIALYSIS EFFLUENT IN EARLY DIAGNOSIS OF PERITONITIS: CASE-CONTROL STUDY IN PERITONEAL DIALYSIS PATIENTS.

♦ Background: Peritoneal dialysis (PD) is frequently complicated by high rates of peritonitis, which result in hospitalization, technique failure, transfer to hemodialysis, and increased mortality. Early diagnosis, and identification of contributing factors are essential components to increasing effectiveness of care. In previous reports, neutrophil gelatinase-associated lipocalin (NGAL), a lipocalin which is a key player in innate immunity and rapidly detectable in peritoneal dialysis effluent (PDE), has been demonstrated to be a useful tool in the early diagnosis of peritonitis. This study investigates predictive value of PDE NGAL concentration as a prognostic indicator for PD-related peritonitis. ♦ Methods: A case-control study with 182 PD patients was conducted. Plasma and PDE were analyzed for the following biomarkers: C-reactive protein (CRP), blood procalcitonin (PCT), leucocytes and NGAL in PDE. The cases consisted of patients with suspected peritonitis, while controls were the patients who came to our ambulatory clinic for routine visits without any sign of peritonitis. The episodes of peritonitis were defined in agreement with International Society for Peritoneal Dialysis guidelines. Continuous variables were presented as the median values and interquartile range (IQR). Mann-Whitney U test was used to compare continuous variables. Univariate and multivariate logistic regression were used to evaluate the association of biomarkers with peritonitis. Receiver operating characteristic (ROC) curve analysis was used to calculate area under curve (AUC) for biomarkers. Finally we evaluated sensitivity, and specificity for each biomarker. All statistical analyses were performed with SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). ♦ Results: During the 19-month study, of the 182 patients, 80 had a clinical diagnosis of peritonitis. C-reactive protein levels (p < 0.001), PCT (p < 0.001), NGAL in PDE (p < 0.001), and white blood cells (WBC) in PDE (p < 0.001) were all significantly different in patients with and without peritonitis. In univariate analysis, CRP (odds ratio [OR] 1,339; p = 0.001), PCT (OR 2,473; p < 0,001), WBC in PDE (OR 3,986; p < 0,001), and NGAL in PDE (OR 36.75 p < 0.001) were significantly associated with episodes of peritonitis. In multivariate regression analysis, only WBC (OR 24.84; p = 0,012), and peritoneal NGAL levels (OR 136.6; p = 0,01) were independent predictors of peritonitis events. Moreover, AUC for NGAL in peritoneal effluent was 0,936 (p < 0.001) while AUC for CRP, PCT, and WBC count in peritoneal effluent were 0,704 (p = 0.001), 0.762 (p = 0.039), 0,975 (p < 0.001), respectively. Finally, combined WBC and peritoneal NGAL test increased the specificity (= 96%) of the single test. ♦ Conclusions: These results identify NGAL in peritoneal effluent as a reliable marker of peritonitis episodes in PD patients. Collectively, our findings demonstrate that the use of peritoneal NGAL cooperatively with current clinical diagnostic tools as a prognostic indicator, presents a valuable diagnostic tool in PD-associated peritonitis.

Contents Vol. 37, 2014

189 Selected Abstracts from the 32nd International Vicenza Course on Hemodialysis and Peritoneal Dialysis Vicenza, June 10–13, 2014 (available online only)

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.