Acute Changes in Serum Creatinine and Kinetic Glomerular Filtration Rate Estimation in Early Phase of Acute Pancreatitis.

In patients with acutely changing kidney function, equations used to estimate glomerular filtration rate (eGFR) must be adjusted for dynamic changes in the concentrations of filtration markers (kinetic eGFR, KeGFR). The aim of our study was to evaluate serum creatinine-based KeGFR in patients in the early phase of acute pancreatitis (AP) as a marker of changing renal function and as a predictor of AP severity. We retrospectively calculated KeGFR on day 2 and 3 of the hospital stay in a group of 147 adult patients admitted within 24 h from the onset of AP symptoms and treated in two secondary-care hospitals. In 34 (23%) patients, changes in serum creatinine during days 1-3 of the hospital stay exceeded 26.5 µmol/L; KeGFR values almost completely differentiated those with increasing and decreasing serum creatinine (area under receiver operating characteristic curve, AUROC: 0.990 on day 3). In twelve (8%) patients, renal failure was diagnosed during the first three days of the hospital stay according to the modified Marshall scoring system, which was associated with significantly lower KeGFR values. KeGFR offered good diagnostic accuracy for renal failure (area under receiver operating characteristic-AUROC: 0.942 and 0.950 on days 2 and 3). Fourteen (10%) patients developed severe AP. KeGFR enabled prediction of severe AP with moderate diagnostic accuracy (AUROC: 0.788 and 0.769 on days 2 and 3), independently of age, sex, comorbidities and study center. Lower KeGFR values were significantly associated with mortality. Significant dynamic changes in renal function are common in the early phase of AP. KeGFR may be useful in the assessment of kidney function in AP and the prediction of AP severity.

Oviductal Oxygen Homeostasis in Patients with Uterine Myoma: Correlation between Hypoxia and Telocytes.

Oxygen balance is crucial for angiogenesis, immunity, and tissue repair. The human oviduct is essential for reproductive function, and any imbalance in homeostasis leads to fertility disturbances and might be a reason for ectopic pregnancy development. Uterine myoma is a widespread benign tumour, which is often accompanied by infertility. Telocytes have been discussed in the contexts of motility, fibrosis development, and angiogenesis. We observed the oviducts from patients with and without uterine myoma, comparing the expression of HIF-1, HO, VEGF and its receptor, NOS, oestrogen, and progesterone receptors by immunolabeling. The myometrial and oviductal telocytes were also compared in both groups. Biochemical analyses were conducted for FSH, LH, AMH, sFlt, oestrogen, and progesterone in blood samples. Patients with uterine myoma have different expressions of sex steroid receptors and an increased number of telocytes. The decreasing VEFG expression was compensated by the rise in the HIF-1 and NOS expression. Blood biochemical analyses revealed a higher progesterone level and lower AMH in patients with uterine myoma. No differences in sFlt, FSH, and LF were observed. Uterine myoma impacts oviduct oxygen homeostasis and might cause fertility disturbances (uterine and oviductal infertility factors).

Acute Phase Proteins and Vitamin D Seasonal Variation in End-Stage Renal Disease Patients.

End-stage renal disease (ESRD) patients are vulnerable to vitamin D deficiency due to impaired renal hydroxylation, low dietary intake and inadequate sun exposure. Vitamin D plays a role in innate and adaptive immunity and its seasonal variation has been linked to mortality. ESRD is associated with inadequate removal of pro-inflammatory cytokines regulating acute phase protein (APP) synthesis. Our aim was to look for associations between lifestyle factors, diet, and vitamin D seasonal variation and their relationship with selected APPs and calcium-phosphate metabolism. The study included 59 ESRD patients treated with maintenance hemodialysis. A 24-hour dietary recall was conducted in the post-summer (November 2018, PS) and post-winter (February/March 2019, PW) period, and blood was collected for the measurements of serum total vitamin D, α1-acid glycoprotein (AGP), C-reactive protein (CRP), albumin, prealbumin (PRE), parathormone, calcium and phosphate. A self-constructed questionnaire gathered information on vitamin D supplementation, sun exposure and physical activity. Higher caloric intake was observed PW compared PS. Less than 15% of participants met the dietary recommendations for energy, protein, fiber, vitamin D and magnesium intake. Vitamin D supplementation was associated with higher serum vitamin D regardless of season. AGP, PRE, albumin, and vitamin D presented seasonal changes (higher values PS). In patients with serum vitamin D below 25 ng/mL, vitamin D seasonal change correlated with CRP and prealbumin change. Phosphate and Ca × P correlated positively with AGP. A low vitamin D serum level could impact the inflammatory process; however, more studies are needed to confirm the relationship.

Serum Urokinase-Type Plasminogen Activator Receptor Does Not Outperform C-Reactive Protein and Procalcitonin as an Early Marker of Severity of Acute Pancreatitis.

Severe acute pancreatitis (SAP) concerns 10⁻20% of acute pancreatitis (AP) patients and is associated with a poor prognosis and high mortality. An early prognosis of the unfavorable outcome, transfer to an intensive care unit (ICU) and the introduction of an adequate treatment are crucial for patients' survival. Recently, the elevated circulating urokinase-type plasminogen activator receptor (uPAR) has been reported to predict SAP with a high diagnostic accuracy among patients in a tertiary center. The aim of the study was to compare the diagnostic utility of uPAR and other inflammatory markers as the predictors of the unfavorable course of AP in patients admitted to a secondary care hospital within the first 24 h of the onset of AP. The study included 95 patients, eight with a SAP diagnosis. Serum uPAR was measured on admission and in the two subsequent days. On admission, uPAR significantly predicted organ failure, acute cardiovascular failure, acute kidney injury, the need for intensive care, and death. The diagnostic accuracy of the admission uPAR for the prediction of SAP, organ failure, and ICU transfer or death was low to moderate and did not differ significantly from the diagnostic accuracy of interleukin-6, C-reactive protein, procalcitonin, D-dimer and soluble fms-like tyrosine kinase-1. In the secondary care hospital, where most patients with AP are initially admitted, uPAR measurements did not prove better than the currently used markers.

Does the Automatic Measurement of Interleukin 6 Allow for Prediction of Complications during the First 48 h of Acute Pancreatitis?

Acute pancreatitis (AP) in most patients takes a course of self-limiting local inflammation. However, up to 20% of patients develop severe AP (SAP), associated with systemic inflammation and/or pancreatic necrosis. Early prediction of SAP allows for the appropriate intensive treatment of severe cases, which reduces mortality. Serum interleukin-6 (IL-6) has been proposed as a biomarker to assist early diagnosis of SAP, however, most data come from studies utilizing IL-6 measurements with ELISA. Our aim was to verify the diagnostic usefulness of IL-6 for the prediction of SAP, organ failure, and need for intensive care in the course of AP using a fully automated assay. The study included 95 adult patients with AP of various severity (29 mild, 58 moderately-severe, 8 severe) admitted to a hospital within 24 h from the onset of symptoms. Serum IL-6 was measured using electochemiluminescence immunoassay in samples collected on admission and on the next day of hospital stay. On both days, patients with SAP presented the highest IL-6 levels. IL-6 correlated positively with other inflammatory markers (white blood cell and neutrophil counts, C-reactive protein, procalcitonin), the markers of renal injury (kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin), and the markers of endothelial dysfunction (angiopoietin-2, soluble fms-like tyrosine kinase-1). IL-6 on admission significantly predicted SAP, vital organ failure, and the need for intensive care or death, with areas under the receiver operating curve between 0.75 and 0.78, not significantly different from multi-variable prognostic scores. The fully automated assay allows for fast and repeatable measurements of serum IL-6, enabling wider clinical use of this valuable biomarker.

Malnutrition, Inflammation, Atherosclerosis Syndrome (MIA) and Diet Recommendations among End-Stage Renal Disease Patients Treated with Maintenance Hemodialysis.

Malnutrition-inflammation-atherosclerosis syndrome is one of the causes of increased mortality in chronic kidney disease (CKD). The aim of the study was to assess the inflammation and nutritional status of patients in end-stage kidney disease treated with maintenance hemodialysis. The study included a group of 98 hemodialyzed patients with stage 5 CKD (38 women and 60 men). Albumin, prealbumin (PRE), and C-reactive protein (CRP) were measured in serum samples collected before mid-week dialysis. Fruit and vegetables frequency intakes were assessed with a questionnaire. CRP was above the reference limit of 5 mg/L in 53% of patients. Moreover, the Glasgow Prognostic Score (GPS) indicated the co-occurrence of inflammation and protein calorie malnutrition in 11% of patients, and the presence of either inflammation or malnutrition in 25%. The questionnaire revealed that hemodialyzed patients frequently exclude fruit and vegetables from their diets. Nearly 43% of the interviewed patients declared frequently eating vegetables, and 35% declared frequently eating fruit, a few times per week or less. The most frequently selected fruit and vegetables had a low antioxidant capacity. The strict dietary restrictions in CKD are difficult to fulfill, and if strictly followed, may lead to protein-calorie malnutrition.

Serum Uromodulin Levels in Prediction of Acute Kidney Injury in the Early Phase of Acute Pancreatitis.

In health, uromodulin is the main protein of urine. Serum uromodulin concentrations (sUMOD) have been shown to correlate with kidney function. Acute kidney injury (AKI) is among the main complications of severe acute pancreatitis (AP). No reports exist on sUMOD in patients with AP, including the diagnostic usefulness for early prediction of AP severity. We measured sUMOD during first 72 h of AP. Sixty-six adult patients with AP were recruited at the surgical ward of the District Hospital in Sucha Beskidzka, Poland. AP was diagnosed according to the Revised Atlanta Classification. Blood samples were collected at 24, 48 and 72 h of AP, and sUMOD concentrations were measured with enzyme-linked immunosorbent test. sUMOD decreased non-significantly during the study. Patients with severe AP had non-significantly lower sUMOD concentrations than those with mild disease. Significant positive correlation was observed between sUMOD and estimated glomerular filtration rate on each day of the study and negative correlations were shown between sUMOD and age, serum creatinine, cystatin C and urea. Patients with AKI tended to have lower sUMOD. Although sUMOD correlated significantly with kidney function in the early phase of AP, measuring sUMOD did not allow to reliably predict AP severity or development of AKI.

Serum Concentrations of Angiopoietin-2 and Soluble fms-Like Tyrosine Kinase 1 (sFlt-1) Are Associated with Coagulopathy among Patients with Acute Pancreatitis.

In severe acute pancreatitis (SAP), systemic inflammation leads to endothelial dysfunction and activation of coagulation. Thrombotic disorders in acute pancreatitis (AP) include disseminated intravascular coagulation (DIC). Recently, angiopoietin-2 and soluble fms-like tyrosine kinase 1 (sFlt-1) were proposed as markers of endothelial dysfunction in acute states. Our aim was to assess the frequency of coagulation abnormalities in the early phase of AP and evaluate the relationships between serum angiopoietin-2 and sFlt-1 and severity of coagulopathy. Sixty-nine adult patients with AP were recruited: five with SAP, 15 with moderately severe AP (MSAP) and 49 with mild AP. Six patients were diagnosed with DIC according to International Society on Thrombosis and Haemostasis (ISTH) score. All patients had at least one abnormal result of routine tests of hemostasis (low platelet count, prolonged clotting times, decreased fibrinogen, and increased D-dimer). The severity of coagulopathy correlated with AP severity according to 2012 Atlanta criteria, bedside index of severity in AP and duration of hospital stay. D-dimers correlated independently with C-reactive protein and studied markers of endothelial dysfunction. Angiopoietin-2, D-dimer, and ISTH score were best predictors of SAP, while sFlt-1 was good predictor of MSAP plus SAP. In clinical practice, routine tests of hemostasis may assist prognosis of AP.

The Diagnostic Usefulness of Serum Total Bile Acid Concentrations in the Early Phase of Acute Pancreatitis of Varied Etiologies.

The most common causes of acute pancreatitis (AP) are biliary tract diseases with cholestasis and alcohol consumption. In 10%-15% of patients, etiology determination is difficult. Identification of the etiology allows for the implementation of adequate treatment. The aim of this study was to assess the utility of the serum concentrations of total bile acids (TBA) to diagnose AP etiology in the early phase of the disease. We included 66 patients with AP, admitted within the first 24 h from the onset of symptoms. TBA were measured in serum at 24, 48, and 72 h from the onset of AP, using an automated fifth generation assay. The bilirubin-to-TBA ratio (B/TBA) was calculated. TBA was highest on the first day of AP and decreased subsequently. In patients with biliary etiology, serum TBA was significantly higher compared to those with alcoholic and other etiologies. B/TBA was significantly higher in patients with alcoholic etiology. At admission, the cut-off values of 4.7 µmol/L for TBA and 4.22 for the B/TBA ratio allowed for a differentiation between biliary and other etiologies of AP with a diagnostic accuracy of 85 and 83%. Both TBA and B/TBA may help in the diagnosis of AP etiology in the early phase of AP.

Determination of serum neutrophil gelatinase-associated lipocalin at the early stage of acute pancreatitis.

AIM: e aim of the study was to assess the diagnostic value of serum concentrations of neutrophil gelatinase-associated lipocalin (sNGAL) for the determination of the severity of acute pancreatitis (AP) at the early stage of the disease. MATERIALS AND METHOD: The study group consisted of 65 patients(34 men and 31 women),aged 62.2 ± 16.0, admitted to the Surgery Department of the District Hospital in Sucha Beskidzka, Poland, with the diagnosis of AP according to the revised Atlanta classification (2012). sNGAL was measured with ELISA at 24, 48 and 72 hours following the onset of AP symptoms. The correlations were analyzed between sNGAL and clinical, as well as laboratory parameters, used for the assessment of AP severity. RESULTS: Severe AP was associated with higher sNGAL at 24, 48 and 72 hours, while moderately severe AP was associated with higher sNGAL at 48 and 72 hours as compared to mild disease. The BISAP score ≥3 during the first 24 hours of hospital stay, and the duration of hospital stay were significantly correlated with sNGAL. Also, sNGAL positively correlated with white blood cells, C-reactive protein and fibrinogen and negatively with albumin throughout the study. The diagnostic accuracy of sNGAL for the differentiation between mild AP and more severe disease was 75%, 77% and 85% at 24, 48 and 72 hours, respectively. CONCLUSIONS: Serum NGAL concentrations are associated with inflammatory markers, BISAP score and the severity of AP. sNGAL may serve as an additional prognostic biomarker in the early assessment of AP severity.

Serum Soluble Fms-Like Tyrosine Kinase 1 (sFlt-1) Predicts the Severity of Acute Pancreatitis.

Organ failure is the most important determinant of the severity of acute pancreatitis (AP). Soluble fms-like tyrosine kinase 1 (sFlt-1) is positively associated with organ failure in sepsis. Our aim was to evaluate the diagnostic utility of automated sFlt-1 measurements for early prediction of AP severity. Adult patients (66) with AP were recruited, including 46 with mild (MAP), 15 with moderately-severe (MSAP) and 5 with severe AP (SAP). Serum and urine samples were collected twice. Serum sFlt-1 was measured with automated electrochemiluminescence immunoassay. Serum concentrations of sFlt-1 were significantly higher in patients with MSAP and SAP as compared to MAP. SAP patients had the highest concentrations. At 24 and 48 h, sFlt-1 positively correlated with inflammatory markers (leukocyte count, C-reactive protein), kidney function (creatinine, urea, cystatin C, serum and urine neutrophil gelatinase-associated lipocalin, urine albumin/creatinine ratio), D-dimer and angiopoietin-2. sFlt-1 positively correlated with the bedside index of severity in AP (BISAP) score and the duration of hospital stay. Serum sFlt-1 above 139 pg/mL predicted more severe AP (MSAP + SAP). In the early phase of AP, sFlt-1 is positively associated with the severity of AP and predicts organ failure, in particular kidney failure. Serum sFlt-1 may be a practical way to improve early assessment of AP severity.

Urine NGAL is useful in the clinical evaluation of renal function in the early course of acute pancreatitis.

INTRODUCTION: Acute Kidney Injury (AKI) is a serious early complications in patients with acute pancreatitis (AP) that signifcantly increases mortality rates compared to patients without AKI. The early diagnosis of AKI during its treatable phases and implementation of appropriate treatment protocols can improve outcomes for this group of patients. A promising biomarker for AKI is neutrophil gelatinase-associated lipocalin (NGAL). AIM: This study evaluated the diagnostic value of NGAL concentrations in serum and in urine for patients developing AKI as an early complication of AP compared to AP patients without AKI. MATERIAL AND METHODS: The study group composed of 65 patients (34 men and 31 women) with a mean age of 62.2 ± 16 years with AP and hospitalized in the Surgery Department of the Direct Hospital in Sucha Beskidzka, Poland between January and December 2014. Serum NGAL (sNGAL) levels were measured with the BioVendor ELISA kit, and urine NGAL (uNGAL) with the Abbott ARCHITECT Analyzer. RESULTS: In the early phase of AP, 11 patients (17%) developed AKI, including 10 patients with stage 1 and one with stage 2. AKI was associated with more severe AP, higher BISAP scores, the need for more intensive treatment, longer hospital stays and higher mortality. Both serum and urine NGAL concentrations were signifcantly higher in patients with AKI throughout the study and signifcantly predicted AKI in simple and multiple logistic regression adjusted for age, sex and comorbidities. Serum and urine NGAL concentrations were signifcantly correlated with levels of serum urea, creatinine, urine albumin, and the maximum change in serum creatinine. Serum and urine NGAL levels also correlated positively with direct neutrophil counts and CRP concentrations throughout the study. CONCLUSIONS: The measurement of NGAL levels, particularly in urine, is simple, easy to interpret, routinely available, and clinically useful in the assessment of dynamic changes in kidney function for patients with AP.

[Urinalysis in patients at the early stage of acute pancreatitis]. / Badanie ogólne moczu u chorych z ostrym zapaleniem trzustki we wczesnej fazie rozwoju choroby.

Urinalysis is a routine and cheap laboratory test that provides clinically useful information in patients with acute abdominal conditions, including acute pancreatitis. The aim of the study was to assess the relationships between the results of urinalysis and the course of the disease among 65 patients with acute pancreatitis (34 men and 31 women, mean age 61 ± 19 years) at the early phase of the disease, i.e. during the first 72 hours from the onset of symptoms. Mild acute pancreatitis was diagnosed in 47 patients, moderately severe in 13 and severe in 5. The most prevalent abnormalities were proteinuria (43% of patients), high urinary bilirubin (20%), erythrocytes (18%), glucose (18%) and leukocytes (17%). High urinary protein and low specific gravity were associated with more severe acute disease and with acute kidney injury. The severity of bilirubinuria and proteinuria were positively correlated with urine concentrations of neutrophil gelatinase associated lipocalin (NGAL). Urinalysis should be routinely performed in patients with acute pancreatitis.

Seasonal effect of vitamin D deficiency in patients with acute myocardial infarction.

BACKGROUND: Vitamin D is a major regulator of mineral bone metabolism. The lower vitamin D levels in patients with acute myocardial infarction (AMI) and the seasonal variation of vitamin D levels are proposed. AIM: The evaluation of the seasonal relationship of 25(OH)D levels in patients with AMI and analysis of confounding factors (gender or diabetes mellitus) affecting the levels of vitamin D in AMI patients. METHODS: Fifty-nine consecutive patients with mean age 58 ± 9.4 years were admitted to the Department of Invasive Cardiology. Subjects had diagnosed uncomplicated myocardial infarction. Blood samples for analysis were collected on patient admission to the cardiac unit after heparin treatment. Samples for routine laboratory tests were immediately processed. For 25(OH)D, the 25-hydroxycholecalciferol test, which measures total vitamin D levels in serum (DRG Instruments GmbH, Marburg, Germany), was applied. RESULTS: Median serum 25(OH)D concentration in AMI patients was below the recommended optimal values 7.1 (2.3-13.3) ng/mL. Fifty-three (89.8%) patients had vitamin D deficiency (VDD) below 20 ng/mL, six (10.2%) patients had suboptimal 25(OH)D levels (between 20 ng/mL and 30 ng/mL), and no one had the recommended reference range. The seasonal effect of 25(OH)D variations among AMI patients was observed with the lowest levels in the beginning of the year (January-March) and the highest levels at the end of the year (September-December) (p = 0.007). Patients with normoglycaemia had significantly higher (9.2 [2.3-16.8] ng/mL) vitamin D levels compared to patients with impaired glucose tolerance (2.3 [2.3-3.9] ng/mL) or diabetes mellitus (8.5 [2.5-13.3] ng/mL) (p = 0.01). CONCLUSIONS: A high prevalence of VDD in AMI patients has been confirmed. Supplementation of vitamin D in AMI patients with hyperglycaemia can bring greater benefits.

Serum pregnancy-associated plasma protein A correlates with inflammation and malnutrition in patients treated with maintenance hemodialysis.

Advanced chronic kidney disease (CKD) leads to complications such as anemia, electrolyte abnormalities, bone and mineral disorder, and malnutrition-inflammation-atherosclerosis (MIA) syndrome, that result in high cardiovascu- lar mortality. One of the biomarkers associated with inflammation and cardiovascular events is pregnancy-associated plasma protein A (PAPP-A). The aim of the study was to measure serum PAPP-A in hemodialyzed CKD patients, and to investigate its correlations with the laboratory markers of the complications. We enrolled 78 consecutive stable adult CKD patients treated with maintenance hemodialysis for median period of 60 months. PAPP-A concentrations were measured with by electrochemiluminescence immunoassay. Average serum PAPP-A in hemodialyzed patients was almost two times higher than the upper reference limit. It positively correlated with N-terminal pro-brain natriuretic peptide (NT-proBNP), serum sodium, and the markers of inflammation and malnutrition. In conclusion, serum PAPP-A seems a useful biomarker associated with cardiovascular dysfunction, inflammatory state and malnutrition in hemodialysis patients.