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.

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 Spearman's 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 30.5months (IQR 19.4-32.7). During follow-up, there were 29 cardiovascular events (39.2%). In univariable analysis, patient's 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.

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 (ß = 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.

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.

Bioelectrical impedance analysis in the assessment of hydration status in peritoneal dialysis patients.

OBJECTIVE: Assessment of fluid status in chronic peritoneal dialysis (PD) patients is complex. Clinical evaluation based solely on body weight, blood pressure, volume of ultrafiltration (UF) and peripheral edema is insufficient. A non-invasive test, bioelectrical impedance analysis (BIA) might be of potential benefit. AIM: To test whether BIA correlates with other ancillary markers of extracellular fluid volume, namely B-type natriuretic peptide (BNP), residual renal function (RRF) and UF, and whether BIA provides complementary information in categorizing PD patients vis-à-vis hydration status. METHODS: A cross-sectional study of 61 out-patients on chronic PD. Single-frequency BIA measurements of resistance/height were divided into tertiles (lowest: <253 Ω/m; middle: >253 Ω/m and <316 Ω/m; highest: >316 Ω/m). RESULTS: Compared to patients in the highest tertile of BIA (least fluid), patients in the lowest tertile (most fluid) had highest BNP, RRF and UF (93.5 vs. 55.0 pg/ml, p = 0.029; 850 vs. 300 ml/day, p = 0.05; and 1.75 vs. 1.21 l/day, p = 0.023, respectively). CONCLUSIONS: BIA tertiles categorized PD patients who differed in BNP, RRF and UF in a stepwise pattern, suggesting BIA may better inform hydration status, and serve as an additional clinical tool in management of chronic PD patients.

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.

Rational choice of peritoneal dialysis catheter.

The peritoneal catheter should be a permanent and safe access to the peritoneal cavity. Catheter-related problems are often the cause of permanent transfer to hemodialysis (HD) in up to 20% of peritoneal dialysis (PD) patients; in some cases, these problems require a temporary period on HD. Advances in connectology have reduced the incidence of peritonitis, and so catheter-related complications during PD have become a major concern. In the last few years, novel techniques have emerged in the field of PD: new dialysis solutions, better connectology, and cyclers for automated PD. However, extracorporeal dialysis has continued to improve in terms of methods and patient survival, but PD has failed to do so. The main reason is that peritoneal access has remained problematical. The peritoneal catheter is the major obstacle to wide-spread use of PD. Overcoming catheter-related problems means giving a real chance to development of the peritoneal technique. Catheters should be as efficient, safe, and acceptable as possible. Since its introduction in the mid-1960s, the Tenckhoff catheter has not become obsolete: dozens of new models have been proposed, but none has significantly reduced the pre-dominance of the first catheter. No convincing prospective data demonstrate the superiority of any peritoneal catheter, and so it seems that factors other than choice of catheter are what affect survival and complication rates. Efforts to improve peritoneal catheter survival and complication rates should probably focus on factors other than the choice of catheter. The present article provides an overview of the characteristics of the best-known peritoneal catheters.

Advances in the technology of automated, tidal, and continuous flow peritoneal dialysis.

Automated peritoneal dialysis (APD) has undergone substantial growth in recent years because of an increased demand for higher doses of peritoneal dialysis (PD) treatment and a need to improve quality of life for patients. The evolution of this treatment is closely linked with the development of new automatic machines and with recent advances in prescription and monitoring of PD treatment. In the present article, we describe the characteristics of the new generation of APD cyclers with particular regard to adequacy targets and safety. There is renewed interest in continuous-flow peritoneal dialysis (CFPD), because of a belief that new peritoneal access technologies will make the success of this modality a possibility. In the CFPD technique, a certain amount of fluid is constantly present in the abdomen, and constant inflow and outflow are maintained without interruption thanks to paired indwelling catheters. The PD solution is used either in a single pass or in a recirculation loop with a regeneration systems (sorbent cartridge or dialyzer).

Integration of peritoneal dialysis in the treatment of uremia.

The real integration of a specific therapy into the renal replacement program is represented by the possibility of easy and free patient transfer from one treatment to another without restrictions. In the case of peritoneal dialysis we feel that its integration in the therapeutic approach of uremia represents an ethical obligation for the physician, a clinical opportunity for the patient and a good cost/benefit solution for care givers. A full conviction that peritoneal dialysis represents a real therapeutic option for ESRD patients is necessary to achieve a real integration of this therapy in the uremia treatment program. A positive cost benefit ratio, both from the clinical and the economical points of view must also be seeked. The patient indirectly, must receive the same positive conviction, based on solid data and clinical results, comparable to those achievable in hemodialysis. Furthermore the patient must know that such treatment will provide an equal opportunity for kidney transplant compared to other therapies. Such a kind of feeling and knowledge must include information on patient's survival, rate of complications, treatment adequacy, availability of different techniques within the treatment and complete summary of advantages and disadvantages.

Evolution of technology for automated peritoneal dialysis.

Automated peritoneal dialysis (APD) is important for the further penetration of PD in the dialysis marketplace. Long dwell, equilibration PD (CAPD) has limited applicability in many patients due to inadequate solute clearance or fast membrane transport characteristics. Providing large volumes of dialysate over circumscribed hours is highly labor intensive without an automated system. Early attempts at APD were crude but effective in reducing labor, which was generally provided by nursing staff. Later evolution of PD technology has been greatly accelerated by the microchip, and by miniaturization of components. Current generation machines allow individualized fill volumes, variable tidal volumes and additional daytime automated exchanges, teledialysis, memorized delivery control, and full portability. The ideal machine should not only be able to perform all treatment schedules, but it should also optimize the performance of a selected treatment strategy. Biocompatible solutions, improved osmotic agents, and sorbent technology are all adaptable to APD. The eventual evolution toward continuous flow PD will resolve many of the current problems with both CAPD and APD.

A new home based bioimpedance system for PD.

Fluid overload and uncontrolled hypertension may be considered important mortality risk factors in peritoneal dialysis (PD) population. Even malnutrition is highly prevalent in PD patients. It is now well established that lower levels of serum markers of nutrition such as albumin, creatinine, and prealbumin are associated with increased mortality in PD patients [Fein, P.A. et al: Adv Perit Dial 2002;18:195-199]. Moreover cardiovascular disease is a leading cause of death in patients with end-stage renal disease, and hypertension and volume expansion are highly prevalent in long-term PD patients. Many studies in hemodialysis and in PD have demonstrated that phase sensitive bioelectrical impedance analysis is a widely used and proven method for evaluating patient's body composition. The vectorial bioimpedance analysis is a validated system to evaluate the hydration and nutritional state of hemodialysis and PD patients with acceptable sensitivity and specificity. The aim of this study is to evaluate the reliability and accuracy of the new multifrequency BodyComp bioimpedance analyzer as a home based tool versus traditional Bia Vector.

APD prescription: achieving the adequacy goals.

In the last few years, automated peritoneal dialysis (APD) has undergone considerable improvements due to technological developments. The definition of a minimal dose of peritoneal dialysis (PD) has not yet been completely assessed. Appropriate use of APD requires an evaluation of dialytic efficiency in terms of dialytic indexes and their targets. Many dialytic treatment modalities have been performed in order to achieve adequacy targets. Some aspects have to be taken into consideration to reach the optimal dialytic dose: optimizing mass transfer in correlation with intraperitoneal volumes, prescribing tailored treatment modalities according to different characteristics of peritoneal membranes and individual patient needs, and performing more biocompatible treatments using different glucose profiling and alternative physiologic PD fluids. New high-flow techniques such as continuous flow PD can ensure better urea and creatinine clearances and ultrafiltration rates, leading to a higher utilization of the APD modality.