Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction. STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines. SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms. SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI. DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis. ANALYTICAL APPROACH: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses. RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively. LIMITATIONS: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

Is everolimus linked to metabolic syndrome in liver transplant recipients?

BACKGROUND: As the mortality rates after liver transplantation (LT) have been reduced, the attention has shifted to additional conditions which still compromise the quality of life and the survival of these patients, such as the post-LT metabolic syndrome (MS). In order to determine the prevalence and the factors associated with the post-LT MS, we carried out the present study. METHODS: One hundred and six LT recipients, after completing at least 1 year follow up after LT, were included in the study. Data on clinical, laboratory parameters and immunosuppressive therapy before and after LT were recorded. MS was defined as per current diagnostic criteria. RESULTS: MS was prevalent in 47.2% (50 of 106 patients) and was not associated with the LT indications and the time period after LT. Univariate analysis showed that history of diabetes mellitus before (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.046-9.918, p = 0.042) and after LT (OR 6.03, 95% CI 2.18-16.67, p = 0.001), the age at the time of baseline visit (OR 1.077, 95% CI 1.033-1.124, p = 0.001) and the everolimus-based immunosuppression (OR 1.23, 95% CI 1.003-1.33, p = 0.019) were significantly associated with MS. Notably, everolimus administration was the only factor independently associated with the presence of post-LT MS (OR 1.026, 95% CI 1.004-1.047, p = 0.019). More specifically, everolimus was linked to the presence of arterial hypertension (OR 1.02, 95% CI 1.0-1.03, p = 0.05) and hyperlipidemia (OR 2.87, 95% CI 1.28-6.56, p = 0.011). CONCLUSIONS: Our study demonstrated for the first time that everolimus was independently associated with post-LT MS. Nevertheless, more robust studies are required to confirm these findings.

Relative Adrenal Insufficiency is Associated with the Clinical Outcome in Patients with Stable Decompensated Cirrhosis.

BACKGROUND: The clinical impact of relative adrenal insufficiency (AI) on patients with stable decompensated cirrhosis (DeCi) has not been yet elucidated. AIM: Explore the association between AI and outcome [death or liver transplantation (LT)] in patients with DeCi. MATERIAL AND METHODS: Patients with DeCi presenting no active complication have been included. Clinical and laboratory data, including serum levels of corticosteroid-binding globulin (CBG), interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNFα) were recorded in each participant. Salivary cortisol (SC) and serum total cortisol (STC) were assessed at (T0) and 1 h (T60) after intravenous injection of 250 µg corticotropin. RESULTS: 113 consecutive patients were totally tested. Median SC was 3.9 ng/mL and 15.5 ng/mL and median STC was 10.7 µg/dL and 22.7 µg/dL at T0 and T60 respectively. The patients with AI [group 1, n = 34 (30%)] had significantly lower systolic blood pressure (106 ± 12 vs. 113 ± 13 mmHg, p = 0.05), serum sodium (133 ± 7 vs. 137 ± 12 mEq/ L, p = 0.04), HDL (29.9 ± 14 vs. 38.6 ± 18 mg/dL, p = 0.034) and albumin (2.7 ± 0.5 vs. 3.1 ± 0.5 g/dL, p = 0.002), but higher direct bilirubin (median: 1.6 vs. 0.8 mg/dL, p = 0.029) compared to those without AI [group 2, n = 79 (70%)]. Moreover, group 1 patients presented more frequently past history of spontaneous bacterial peritonitis (SBP) [10/34 (29.4%) vs. 6/79 (7.5%), p = 0.002]. AI was significantly associated with death [HR = 2.65, 95% C.I.: 1.55 - 4.52, p = 0.003 over a follow up period of 12 (6-48) months.] Conclusions. The presence of AI in patients with stable DeCi predispose to obvious clinical implications since it is associated with circulatory dysfunction, previous history of SBP and worse survival.

Interferon-free regimens in patients with hepatitis C infection and renal dysfunction or kidney transplantation.

Treatment of patients with chronic kidney disease (CKD) and chronic hepatitis C (CHC) differs from that used in the general CHC population mostly when glomerular filtration rate (GFR) is below 30 mL/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvir-based regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response (SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current management of CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice.

Comparison of creatinine clearance estimates in subgroups based on Body Mass Index and albumin.

BACKGROUND: The establishment of accurate equations for glomerular filtration rate (GFR) estimations is still far from the realization. Factors such as age, diabetes, stage of CKD, pregnancy, muscle mass and ethic nation are associated with less reliance upon commonly utilized estimation equations. We aimed to compare the routine use of 24-hour creatinine clearance (CrCl) and GFR estimates calculated by Crockoft-Gault (CG) and modification of diet in renal disease (MDRD) formulas in patients with different levels of renal dysfunction in subgroups, based on Body Mass Index (BMI) and serum albumin (Alb) levels. METHODS: Two hundred and seventy-nine non diabetic patients (172 men and 107 women), aged 54±23 years, with BMI 27.3±4.4 were enrolled in the study. All patients presented creatinine 1.8±1.2 (mg/dL) and Alb 3.5±1.3g/dL. The comparison of CrCl versus CG had bias 3.1 while the comparison of CrCl versus MDRD had a bias of 6.6. RESULTS: Univariate analysis showed that age, sex and BMI were not significant biases related to the CG, MDRD and CrCl. Indeed, the bias related to the CG was significantly lower than that related to MDRD in patients with either low or high serum albumin. Interestingly, the bias associated with CG was 1.3 in non-diabetic patients with Alb ≤3.5 mg /dL suggesting that CG equation could be used interchangeable to CrCl in these patients. CONCLUSION: CG gave a better prediction of measured CrCl than MDRD in Mediterranean, non-diabetic, non-hospitalized patients although misclassification of patients with regard to renal impairment stage was not present.

Microcirculatory alterations during continuous renal replacement therapy in ICU: A novel view on the 'dialysis trauma' concept.

OBJECTIVE: The purpose of this study was to evaluate microcirculation over 24 h renal replacement therapy (CRRT) in critically ill patients. METHODS: We conducted a single-center, prospective, observational study, measuring microcirculation parameters, monitored by near infrared spectroscopy (NIRS) before hemodiafiltration onset (H0), and at six (H6) and 24 h (H24) during CRRT in critically ill patients. Serum Cystatin C (sCysC) and soluble (s)E-selectin levels were measured at the same time points. Twenty-eight patients [19 men (68%)] were included in the study. RESULTS: Tissue oxygen saturation (StO2, %) [76.5 ± 12.5 (H0) vs 75 ± 11 (H6) vs 70 ± 16 (H24), p = 0.04], reperfusion rate, indicating endothelial function (EF, %/sec) [2.25 ± 1.44 (H0) vs 2.1 ± 1.8 (H6) vs 1.6 ± 1.4 (H24), p = 0.02] and sCysC (mg/L) [2.7 ± 0.8 (H0) vs 2.2 ± 0.6 (H6) vs 1.8 ± 0.8 (H24), p < 0.0001] significantly decreased within the 24 h CRRT. Change of EF positively correlated with changes of sCysC within 24 h CRRT (r = 0.464, p = 0.013) while in patients with diabetes the change of StO2 correlated with dose (r = − 0.8, p = 0.01). No correlation existed between hemoglobin and temperature changes with the deteriorated microcirculation indices. sE-Selectin levels in serum were elevated; no difference was established over the 24 h CRRT period. A strong correlation existed between the sE-Selectin concentration change at H6 and H24 and the mean arterial pressure change in the same period (r = 0.77, p < 0.001). CONCLUSIONS: During the first 24 h of CRRT implementation in critically ill patients, deterioration of microcirculation parameters was noted. Microcirculatory alterations correlated with sCysC changes and with dose in patients with diabetes.

Pharmaceutical management of hepatitis B and C in liver and kidney transplant recipients.

The combination of hepatitis B immune globulin with entecavir or tenofovir (at least for a certain period of time) seems to be the most reasonable prophylaxis against recurrent hepatitis B after liver transplantation. Entecavir represents an attractive option for treatment of naïve kidney transplant recipients, because of its high efficacy and the low rates of resistance. However antiviral treatment should be individualized in the view of kidney function and the previous resistance. To date, new captivating therapeutic strategies could make interferon-free regimens viable for treatment of hepatitis C virus positive liver transplant recipients. The recent combinations of sofosbuvir with simeprevir or daclatasvir or ledipasvir plus/minus ribavirin have boosted the on treatment and sustained virological response to rates approaching 100% within liver transplant recipients with recurrent chronic hepatitis C (CHC). Preliminary data showed that the second generation direct oral antivirals could result to high treatment rates of recurrent CHC in kidney transplant recipients as well. Ongoing studies will clarify the optimal treatment of recurrent CHC in kidney transplant recipients.

Interferon-free regimens for the treatment of hepatitis C virus in liver transplant candidates or recipients.

The goal of therapy in chronic hepatitis C virus (HCV) infection is sustained virological response (SVR) which reflects HCV eradication. Treatment against HCV has dramatically improved with the recent availability of direct-acting antivirals (DAAs) including sofosbuvir, simeprevir, daclatasvir, ledipasvir/sofosbuvir, paritaprevir/ombitasvir and dasabuvir. Carefully selected combinations of these DAAs offer the potential for highly effective all-oral safe regimens even for patients with decompensated cirrhosis or liver transplant (LT) recipients. Like all current protease inhibitors, simeprevir and paritaprevir should not be used in patients with Child C cirrhosis, while sofosbuvir and ledipasvir/sofosbuvir should not be given in patients with severe renal impairment and glomerular filtration rate less than 30 mL/min. Drug-drug interactions may still occur with the current DAAs particularly in post-LT patients, in whom simeprevir should not be co-administered with cyclosporine and dose adjustments of calcineurin inhibitors are required in case of regimens including the ritonavir boosted paritaprevir. Phase II clinical trials and real life cohort studies have shown that sofosbuvir based combinations are safe and can achieve improvements of clinical status, high SVR rates and even prevention of post-LT HCV recurrence in patients with decompensated cirrhosis or LT-candidates. In the post-LT setting, sofosbuvir based regimens and the combination of paritaprevir/ombitasvir and dasabuvir have been reported to be safe and achieve high SVR rates, similar to those in non-transplant patients, being effective even in cases with cholestatic fibrosing hepatitis. Ongoing clinical trials and rapidly emerging real life data will further clarify the safety and efficacy of the new regimens in these settings.

Treatment of chronic hepatitis C in liver transplant candidates and recipients: Where do we stand?

The first generation direct antiviral agents (DAAs) highlighted substantial prognosis improvement among liver transplant (LT) candidates and recipients with recurrent hepatitis C virus (HCV) infection. During 2014, second generation DAAs are associated with high sustained virological response rates (> 95%), shortened duration courses and relatively few toxicities. In keeping with the currently available data, patients with decompensated cirrhosis awaiting LT is preferable to be treated with interferon-free, new generation DAAs, with or without ribavirin combinations. Although data about the safety of new DAAs combinations in this patient population are limited, sofosbuvir and daclatasvir pharmacokinetics do not appear to change significantly in moderate or severe liver impairment, while other new DAAs (simeprevir, asunaprevir) seem to be contraindicated in patients with severe liver impairment (Child-Pugh class C). On the other hand, sofosbuvir should not be given in patients with glomerular filtration rate ≤ 30 mL/min, but ongoing trials will clarify better this issue. With the objective that newer antiviral combinations will yield safer and more efficient manipulation of HCV recurrence post-transplant, the European Association for the Study of the Liver has recently updated its recommendations towards this direction. Nevertheless the new antivirals' high cost may be the biggest challenge to their implementation worldwide.

Changes in skeletal muscle microcirculation after a hemodialysis session correlates with adequacy of dialysis.

BACKGROUND: Monitoring of the microcirculation may add additional information in terms of improving the adequacy of hemodialysis (HD) for patients. Withdrawal of liquid and complement activation during a HD session reduces the external pressure on the microcirculation and leads to an increased dilatation of the peripheral capillaries. The purposes of this study were to assess the effect of a single HD or hemodiafiltration session on the thenar microcirculation in patients with end-stage renal disease (ESRD) with or without diabetes, investigate the possible relationship between changes in the microcirculation and adequacy of dialysis (including Kt/V and parameters indicating secondary hyperparathyroidism), and compare microcirculation measurements obtained from patients with ESRD and those from healthy controls. METHODS: This pilot prospective observational study including eleven patients with ESRD on maintenance HD (nine men of mean age 73±10.5 years, ten [91%] with hypertension), nine patients with ESRD on maintenance hemodiafiltration (six men of mean age 65.5±13.2 years, five [55.5%] with diabetes and four [44.5%] with hypertension), and eight healthy volunteers. Two paired microcirculation assessments were recorded for each HD patient before and after a dialysis session. Near infrared spectroscopy and the vascular occlusion test were used to assess the microcirculation, and blood work samples were collected before and after dialysis when the pump slowed down. RESULTS: Patients with ESRD showed an increase in thenar cell metabolism at rest after a 4-hour HD session, and changes in cell metabolism correlated with the Kt/V of the session. Pre-dialysis tissue oxygen saturation over the 4-hour HD session correlated with pre-dialysis serum calcium and parathyroid hormones. Vascular reactivity was lower in ESRD patients receiving HD or hemodiafiltration than in healthy controls. CONCLUSION: Improvement in skeletal muscle microcirculation noted after a HD session was related to adequacy of dialysis. Evaluation of the microcirculation may provide additional information for management of patients on HD and identify novel targets for treatment. These preliminary findings need to be tested using a larger data set.

Adrenal insufficiency in patients with decompensated cirrhosis.

Adrenal reserve depletion and overstimulation of the hypothalamus-pituitary-adrenal (HPA) axis are causes for adrenal insufficiency (AI) in critically ill individuals. Cirrhosis is a predisposing condition for AI in cirrhotics as well. Both stable cirrhotics and liver transplant patients (early and later after transplantation) have been reported to present AI. The mechanisms leading to reduced cortisol production in cirrhotics are the combination of low cholesterol levels (the primary source of cortisol), the increased cytokines production that overstimulate and exhaust HPA axis and the destruction of adrenal glands due to coagulopathy. AI has been recorded in 10%-82% cirrhotics depending on the test used to evaluate adrenal function and in 9%-83% stable cirrhotics. The similarity of those proportions support the assumption that AI is an endogenous characteristic of liver disease. However, the lack of a gold standard method for AI assessment and the limitation of precise thresholds in cirrhotics make difficult the recording of the real prevalence of AI. This review aims to summarize the present data over AI in stable, critically ill cirrhotics and liver transplant recipients. Moreover, it provides information about the current knowledge in the used diagnostic tools and the possible effectiveness of corticosteroids administration in critically ill cirrhotics with AI.

Management of patients with hepatitis B in special populations.

The development of effective nucleos(t)ide analogs (NAs) against hepatitis B virus (HBV) has improved the outcome of patients with chronic hepatitis B (CHB). This review updates issues related to the management of CHB patients included in special populations. Entecavir (ETV) and tenofovir (TDF) represent the currently recommended first-line NAs in patients with HBV decompensated cirrhosis. The combination of HBV immunoglobulin (usually for a finite duration) and NA is considered the standard of care for prophylaxis against HBV recurrence after liver transplantation. TDF is the best choice for hemodialysis patients and in patients with chronic kidney disease with nucleoside resistance. ETV and telbivudine are the preferred options in naïve renal transplant recipients and with low viremia levels, respectively. All hepatitis B surface antigen (HBsAg)-positive candidates should be treated with NAs before renal transplantation to achieve undetectable HBV DNA at the time of transplantation. Conventional interferon or NAs can also be used in children, on the basis of well-established therapeutic indication. Pregnant women at high risk of perinatal transmission could be treated with lamivudine, telbivudine or TDF in the last trimester of pregnancy. HBsAg-positive patients under immunosuppression should receive NA pre-emptively (regardless of HBV DNA levels) up to 12 mo after its cessation. In HBsAg negative, anti-HBc positive patients under immunosuppression, further studies are needed to form a final conclusion; however, it seems that anti-HBV prophylaxis is justified in such patients with hematological diseases and/or for those receiving rituximab-containing regimens, regardless of their anti-HBs or serum HBV DNA status.

Renal dysfunction in patients with cirrhosis: Where do we stand?

Patients with cirrhosis and renal failure are high-risk patients who can hardly be grouped to form precise instructions for diagnosis and treatment. When it comes to evaluate renal function in patients with cirrhosis, determination of acute kidney injury (AKI), chronic kidney disease (CKD) or AKI on CKD should be made. First it should be excluded the prerenal causes of AKI. All cirrhotic patients should undergo renal ultrasound for measurement of renal resistive index in every stage of liver dysfunction and urine microscopy for differentiation of all causes of AKI. If there is history of dehydration on the ground of normal renal ultrasound and urine microscopy the diuretics should be withdrawn and plasma volume expansion should be tried with albumin. If the patient does not respond, the correct diagnosis is HRS. In case there is recent use of nephrotoxic agents or contrast media and examination shows shock, granular cast in urinary sediment and proteinuria above 0.5 g daily, acute tubular necrosis is the prominent diagnosis. Renal biopsy should be performed when glomerular filtration rate is between 30-60 mL/min and there are signs of parenchymal renal disease. The acute renal function is preferable to be assessed with modified AKIN. Patients with AKIN stage 1 and serum creatinine ≥ 1.5 mg/dL should be at close surveillance. Management options include hemodynamic monitoring and management of fluid balance and infections, potentially driving to HRS. Terlipressin is the treatment of choice in case of established HRS, administered until there are signs of improvement, but not more than two weeks. Midodrine is the alternative for therapy continuation or when terlipressin is unavailable. Norepinephrine has shown similar effect with terlipressin in patients being in Intensive Care Unit, but with much lower cost than that of terlipressin. If the patient meets the requirements for transplantation, dialysis and transjugular intrahepatic portosystemic shunt are the bridging therapies to keep the transplant candidate in the best clinical status. The present review clarifies the latest therapeutic modalities and the proposed recommendations and algorithms in order to be applied in clinical practice.

Caregivers' experience in patients with chronic diseases.

The aim of this study was to describe the characteristics of caregivers of patients with chronic diseases, assess their perceived burden, and investigate factors influencing this burden. Seventy-three patient-attendants (43 men and 30 women) participated in the pilot-research conducted by two clinics. Of them, 68% attended patients with a malignant disease and 32% attended patients in the end stage of renal disease. Based on questionnaire data, the influence of the social support was studied, in particular that of family members or through state programmers. Family members are the primary caregivers (spouses 51%, children 29%, and others 20%). Psychological support is the main important help that they need and there are a small number of caregivers who have access to a network of medical and social support. It is found that the family still remains the main supporting mechanism for attendants and patients in our population.

Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation.

New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.

Prediction of the renal replacement therapy requirement in mechanically ventilated critically ill patients by combining biomarkers for glomerular filtration and tubular damage.

PURPOSE: Mechanically ventilated critically ill patients with high severity score indices need a very cautious therapeutic approach. Considering that inappropriate decisions on renal replacement therapy (RRT) initiation may promote unwanted adverse effects, we evaluated whether a panel of novel and traditional renal markers is superior to conventional renal marker in predicting RRT requirements in this group of patients. METHODS: This was a prospective observational study, performed at the two distinct multidisciplinary intensive care units (ICUs) of a 1000-bed tertiary hospital. Of 310 consecutive patients, 106 patients fulfilled the inclusion criteria of the study. Urinary neutrophil gelatinase-associated lipocalin (uNGAL), serum creatinine (sCr) and serum cystatin C (sCysC) were determined on ICU admission. The predictive performance of all markers for first RRT was tested and compared based on the area under the receiver operating characteristic (ROC) curves. Time-dependent ROC curves were used to assess the earlier time point where the markers presented their maximum area under the curve (AUC). RESULTS: All studied biomarkers and acute physiology and chronic health evaluation (APACHE) II score, were significant independent predictors of RRT (uNGAL-AUC=0.73, sCysC-AUC=0.76, sCr-AUC=0.78, APACHE-AUC=0.73, P<0.0001). sCysC and sCr showed early maximum predictive ability within 10 days of ICU admission, while uNGAL and APACHE II score within 11 days of ICU admission. sCr combined with normalized (n)NGAL and sCysC combined with either nNGAL or uNGAL established best predictors for the RRT initiation (AUC-ROC=0.8). Distinguishing patients without acute kidney injury (AKI) on ICU entry, the combination of sCysC and APACHE II score proved best (AUC-ROC=0.78). CONCLUSIONS: Specific markers of kidney dysfunction and of kidney damage can be successfully combined to increase the prognostic capability for RRT initiation. The presence of AKI affects diagnostic performance. Without an established AKI on ICU admission, future RRT requirement was better predicted by the combination of illness severity with a marker of glomerular filtration rate. With AKI on ICU admission a combination of the marker of glomerular filtration rate with one of tubular injury proved best.

Hyponatremia in peritoneal dialysis: epidemiology in a single center and correlation with clinical and biochemical parameters.

BACKGROUND: Hyponatremia in peritoneal dialysis (PD) patients has previously been associated with water overload and weight gain, or with malnutrition and intracellular potassium depletion. Although there is a sizable literature about transmembrane sodium and water removal in PD, there are few reports about the incidence and characteristics of hyponatremia in the clinical setting. AIM: We evaluated the incidence and factors associated with hyponatremia in PD patients in a single PD unit. METHODS: We retrospectively evaluated the records of all patients (n = 198) who were treated with PD in the Home PD Unit of the University Health Network at Toronto General Hospital during 2010. We identified 166 patients who had a minimum follow-up of 60 days during 2010 and at least 2 consecutive sodium measurements at least a month apart. We examined baseline differences between patients who developed hyponatremia and those who did not, and clinical and biochemical factors that correlated with mean sodium values. In the 24 patients who developed hyponatremia, we examined paired differences between the normonatremic and hyponatremic periods. Finally, we investigated any possible correlations of change in serum sodium with clinical and biochemical characteristics before and during the hyponatremic period. RESULTS: The incidence of hyponatremia was 14.5%. In multivariate analysis, serum sodium correlated significantly and independently with residual renal function (RRF: r = 0.463, p = 0.0001) and negatively with the daily volume of instilled icodextrin (r = -0.476, p = 0.0001). Residual renal function was significantly lower in patients with hyponatremia than in those with normal serum sodium (1.97 ± 2.3 mL/min vs 4.31 ± 5.01 mL/min, p = 0.033). The mean paired difference in body weight was -1.113 kg and the median difference was -0.55 kg (range: -8.5 kg to +4.2 kg). Impressively, hyponatremia was not associated with an increase in body weight in most patients who developed this complication (13 of 16 for whom comparative weights were known). Moreover, the mean paired change in serum sodium (ΔNa) from normonatremia to hyponatremia was, contrary to our expectations, significantly correlated with a decrease in body weight (r = 0.584, p = 0.017). The ΔNa was also significantly correlated with serum potassium (r = 0.526, p = 0.008), the greatest drop in serum sodium being associated with lower serum potassium in the hyponatremic period, as predicted. CONCLUSIONS: Hyponatremia is seen more often than expected in a clinical setting. Serum sodium is strongly correlated with RRF, hyponatremia being associated with lower RRF. In patients who experienced hyponatremia, the fall in serum sodium was associated with a decrease, not an increase, in body weight and was correlated with serum potassium, suggesting that sodium and potassium depletion-and, by inference, malnutrition-may be important contributors in the clinical setting.