Jacek S. Malyszko

Neutrophil-Gelatinase-Associated Lipocalin and Renal Function after Percutaneous Coronary Interventions

Background/Aims: The value of neutrophil-gelatinase-associated lipocalin (NGAL), a novel biomarker in the detection of acute renal failure in children after cardiac surgery, has been highlighted in previous studies. The incidence of percutaneous coronary intervention (PCI) increases, which may possibly result in increased incidences of contrast nephropathy, its potentially serious complication. Therefore, the aim of our study was to assess prospectively NGAL in patients undergoing elective PCI in relation to serum creatinine. Methods: NGAL was assessed in the serum and urine using commercially available kits. Results: We measured urinary and serum NGAL before, and 2, 4, 12, 24 and 48 h after PCI. We found a significant rise in serum NGAL 2 and 4 h after PCI, and a rise in urinary NGAL 4 and 12 h after PCI. Before PCI, serum NGAL was significantly associated with serum creatinine, urea, urinary NGAL, hemoglobin, hematocrit, albumin, age and presence of diabetes. In multivariate analysis, serum creatinine was the only predictor of serum NGAL. Serum NGAL 2 h after PCI correlated with serum creatinine, duration of PCI, HbA1c, hematocrit, hemoglobin and urinary NGAL. In multivariate analysis, the only predictors of serum NGAL 2 h after PCI were serum creatinine, time of PCI and HbA1c. Serum NGAL before PCI was significantly higher in diabetics than in non-diabetics. Conclusions: NGAL may represent a sensitive early biomarker of renal impairment after PCI. Serum creatinine, duration of PCI, but not type and amount of contrast agent, and appropriate treatment of diabetes, reflected by HbA1c, predict a rise in serum NGAL and kidney function following PCI.

Could neutrophil-gelatinase-associated lipocalin and cystatin C predict the development of contrast-induced nephropathy after percutaneous coronary interventions in patients with stable angina and normal serum creatinine values?

The value of neutrophil-gelatinase-associated lipocalin (NGAL) was highlighted as a novel biomarker for the detection of acute renal failure. We tested the hypothesis whether NGAL could represent an early biomarker of contrast-induced nephropathy (CIN) in 100 patients with normal serum creatinine values undergoing percutaneous coronary interventions (PCI). In addition, we assessed serum and urinary NGAL in relation to cystatin C, estimated glomerular filtration rate, and serum and urinary creatinine in these patients. We measured urinary and serum NGAL values before and 2, 4, 8, 24, and 48 h after the PCI. We found a significant rise in serum NGAL levels 2, 4, and 8 h after the PCI and in urinary NGAL values 4, 8, and 24 h after a PCI procedure. Cystatin C rose significantly 24 h after the procedure. The prevalence of CIN was 11%. The NGAL levels were significantly higher 2 h after the PCI (serum NGAL) or 4 h after the PCI (urinary NGAL), whereas the cystatin C values were higher only 8 and 24 h after a PCI procedure in patients with CIN. In multivariate analysis, only serum creatinine was a predictor of serum NGAL before a PCI. NGAL may represent a sensitive early biomarker of renal impairment after PCI. Serum creatinine level, the presence of diabetes, and the duration of the PCI may affect serum NGAL values and kidney function following a PCI procedure.

Neutrophil gelatinase-associated lipocalin is a new and sensitive marker of kidney function in chronic kidney disease patients and renal allograft recipients.

BACKGROUND/AIMS Few biomarkers exist to monitor chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL), a member of lipocalin family, has recently been proven useful to quantitate CKD. The aim of the study was to assess whether NGAL could represent a novel, sensitive marker of kidney function in adult patients with CKD and in kidney transplant recipients. METHODS We studied possible relations between serum NGAL, creatinine, and estimated glomerular filtration rate (eGFR) in 80 nondiabetic patients with CKD stages 2 to 4; 80 nondiabetic kidney transplant recipients on a calcineurin inhibitor mycophenolate mofetil, or azathioprine as well as prednisone and in healthy volunteers (n = 32, mean age 50 years). RESULTS Serum NGAL and creatinine values were significantly higher and eGFR significantly lower in kidney allograft recipients and patients with CKD compared with controls. NGAL rose gradually, reaching the higher value in stage 4 CKD. In univariate analysis serum NGAL was related to serum creatinine, hemoglobin, hematocrit, leukocyte count, and eGFR. Predictors of serum NGAL were creatinine and eGFR among patients with CKD. On univariate analysis serum NGAL was related to serum creatinine, urea, hemoglobin, hematocrit, white blood cell count, calcineurin concentration, eGFR, and albumin in kidney transplant recipients. On multiple regression analysis, predictors of NGAL were creatinine, calcineurin concentration, and high-sensitivity C-reactive protein. In healthy volunteers, serum NGAL correlated with age, serum creatinine, eGFR, and leukocyte count. CONCLUSION NGAL should be investigated as a potential early, sensitive marker of kidney impairment/injury, which might provide an additional accurate measure of kidney impairment in CKD and among transplant recipients, particularly at advanced stages.

Urinary and Serum Biomarkers after Cardiac Catheterization in Diabetic Patients with Stable Angina and without Severe Chronic Kidney Disease

Background/Aims. Different serum and urinary biomarkers have been recently proposed to serve as markers of acute kidney injury. We tested the hypothesis whether NGAL and other biomarkers could represent an early biomarker of contrast nephropathy (CIN) in diabetic patients with normal serum creatinine undergoing cardiac catheterization in comparison with non-diabetic patients. Methods. Serum, urinary NGAL, cystatin C, urinary kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and liver-type fatty acid binding protein (L-FABP) were evaluated before and 2, 4, 8, 24, and 48 hours after cardiac catheterization using commercially available kits. Results. In both groups we found a significant rise in serum NGAL after 2, 4, and 8 hours, and in urinary NGAL and IL-18 after 4, 8, and 24 hours after cardiac catheterization. Serum cystatin C increased significantly 8 hours, reaching peak 24 hours after cardiac catheterization in both groups, and then decreased after 48 hours. L-FABP and KIM-1 increase significantly after 24 and 48 hours after cardiac catheterization. Conclusions. CIN was similarly prevalent in both diabetic and non-diabetic patients undergoing cardiac catheterization. NGAL seems to be a potential early marker for nephrotoxicity and predictor of contrast nephropathy. It is particularly important in the upcoming setting of short-time hospitalizations for cardiac catheterization.

Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in patients with chronic heart failure and coronary artery disease.

Heart failure and chronic kidney disease share a number of risk factors and pathophysiological pathways. Renal insufficiency is common in patients with chronic heart failure (CHF). The aim of the study was to assess whether neutrophil gelatinase-associated lipocalin (NGAL) could represent a novel, sensitive marker of kidney function in adult patients with chronic heart failure and normal serum creatinine. The study was performed on 150 patients with chronic heart failure due to coronary artery disease. Serum and urinary NGAL as well as serum cystatin C were measured using commercially available kits. Serum NGAL was related, in univariate analysis, to serum creatinine, urinary NGAL, hemoglobin, hematocrit, leukocyte count, eGFR, cystatin C. Urinary NGAL correlated with age, hemoglobin, hematocrit, serum creatinine, eGFR. In multiple regression analysis predictors of serum NGAL were NYHA class, cystatin C, and eGFR. Taking into consideration the fact that the recent DOQI states that individuals with a reduced GFR is at greater risk for cardiovascular disease and cardiac deaths, precise evaluation of renal function is important in order to select the appropriate strategy to reduce the cardiovascular risk. NGAL should be investigated as a potential early and sensitive marker of kidney impairment/injury.

The coagulo-lytic system and endothelial function in cyclosporine-treated kidney allograft recipients

Since thromboembolic complications in transplanted patients are generally attributed to combined abnormalities in platelets and coagulo-lytic system, some hemostatic parameters tPA (tissue plasmogin activator):Ag and activity, its inhibitor-PAIAg and activity, tPA/PAI, thrombin-antithrombin (TAT) and plasmin-antiplasmin complexes (PAP), urokinase-uPA, euglobulin clot lysis time-ECLT, fibrinogen, plasminogen, protein C activity, D-dimer, prothrombin fragments1+2 (F1+2), fibrin monomers, fibronectin, lipoprotein-a, and von Willebrand factor(vWF), were evaluated using commercially available kits. The studies were performed on kidney transplant recipients treated with CsA, azathioprine and prednisone (n=21), and healthy volunteers (n=21). ECLT was significantly prolonged in kidney transplant recipients together with a rise in F1+2,lipoprotein-a, fibrinogen, fibronectin, and vWF when compared with controls. The TPA level was lower, whereas the PAI level was higher in kidney transplant recipients when compared with controls. In conclusion, CsA-treated kidney transplant recipients show evidence of pronounced impairment in fibrinolysis and endothelial damage in comparison with healthy volunteers.

Serum Neutrophil Gelatinase-Associated Lipocalin as a Marker of Renal Function in Non-Diabetic Patients with Stage 2–4 Chronic Kidney Disease

The current Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines advocate creatinine-based equations for estimating GFR to identify patients with potential kidney disease and classify them into different stages due to the fact that serum creatinine is very insensitive to changes in the glomerular filtration rate. Very few biomarkers exist for monitoring chronic kidney disease. The aim of the study was to assess whether NGAL could represent a novel, sensitive marker of kidney function in adult patients with CKD. The study was performed on 92 non-diabetic patients with CKD stages 2–4. Serum and urinary NGAL as well as serum cystatin C were measured using commercially available kits. Serum NGAL was related, in univariate analysis, to serum creatinine, urinary NGAL, hemoglobin, hematocrit, leukocyte count, eGFR, and cystatin C. Urinary NGAL correlated with age, hemoglobin, hematocrit, serum creatinine, and eGFR. In multiple regression analysis, predictors of serum NGAL were creatinine (beta value = 0.97, p = 0.005), cystatin C (beta = 0.34, p = 0.01), and eGFR (beta value = 1.77, p = 0.001). In the healthy volunteers, serum NGAL correlated with age, serum creatinine, eGFR, leukocyte count, and cystatin C. Taking into consideration the fact that the recent DOQI (Dialysis Outcomes Quality Initiative) states that individuals with reduced GRF (glomerular filtration rate) are at greater risk for CVD and cardiac deaths, precise evaluation of renal function is important in order to select the appropriate strategy to reduce the cardiovascular risk. NGAL should be investigated as a potential early and sensitive marker of kidney impairment/injury.

Is Hepcidin a Link between Anemia, Inflammation and Liver Function in Hemodialyzed Patients?

Background: Hepcidin synthesis in hepatocytes is modulated in response to anemia, hypoxia or inflammation. A cross-sectional study was performed to assess hepcidin correlations with markers of iron status, erythropoietin therapy and markers of inflammation in hemodialyzed patients and in the healthy volunteers. Methods: Iron status, complete blood count, creatinine, albumin, lipids were assessed using standard laboratory methods. Hepcidin and high-sensitivity CRP were measured using commercially available kits. Results: Serum iron, TIBC, TSAT, erythrocyte count, Hb, Ht, platelet count, albumin, and cholesterol were lower, whereas ferritin and hepcidin were higher in hemodialyzed patients over controls. Hepcidin correlated positively with triglycerides, albumin, aspartate aminotransferase, lymphocyte count, ferritin and erythropoietin dose and negatively with erythrocyte count, Hb, and Ht in hemodialyzed patients. In multiple regression analysis, triglycerides (β value was 0.28, p = 0.02) and albumin (β value was –0.31, p = 0.006) were correlates of hepcidin in hemodialyzed patients. Conclusions: Elevated hepcidin levels in hemodialyzed patients may be due to functional iron deficiency and anemia. Liver plays an important role in the synthesis of hepcidin. Low-grade inflammation, frequently found in hemodialyzed patients, might also contribute to elevated hepcidin concentration. Hypothesis that hepcidin might link anemia, inflammation and liver function in kidney disease should be further evaluated.

HEMOSTASIS, PLATELET FUNCTION AND SEROTONIN IN ACUTE AND CHRONIC RENAL FAILURE

A pathogenetic role for fibrin deposition and platelet activation in the kidney is thought to play a role in the pathogenesis of acute renal failure (ARF). Thus, some fibrinolytic parameters and platelet function have been studied in 17 patients with ARF and compared to healthy volunteers and subjects with chronic renal failure (CRF). Since serotonin may participate in pathological processes resulting from platelet/vessel wall interactions, its level in the whole blood and plasma was also assayed. In ARF and CRF platelet aggregatory responses in both whole blood and in platelet rich plasma upon stimulation with various agonists (collagen, arachidonic acid, ADP, ristocetin) were lower than those obtained in healthy volunteers. Increased levels of lipoprotein (a), von Willebrand factor (vWF) and fibronectin were found in ARF relative to controls. Protein C activity was significantly lower in patients with ARF. Euglobulin clot lysis time was prolonged in ARF and CRF, reflecting a decreased overall fibrinolytic activity. Activity of tissue plasminogen activator (tPA) inhibitor (PAI) and PAI:Ag were higher in ARF, whereas tPA:Ag, urokinase, tPA/PAI complexes, thrombin-antithrombin complexes (TAT), plasmin-antiplasmin (PAP) complexes, fibrinogen, and F1+2 did not differ between ARF and controls. In CRF elevated levels of TAT, PAP, fibrinogen and prothrombin fragments F1+2 were found, whereas concentration of fibronectin was lowered when compared to controls. In both groups of renal failure patients increased levels of fibrin monomers and d-dimer were found relative to healthy volunteers. Whole blood serotonin was significantly lower, whereas plasma serotonin was significantly higher in patients with ARF and CRF relative to controls. Serotonin uptake and its release from platelets were markedly diminished in patients with ARF and CRF. Chronic renal failure exhibit a slightly different pattern of coagulopathies that acute renal failure.

Accumulation of toxic products degradation of kynurenine in hemodialyzed patients

In patients that developed a chronic renal failure the augmentation intryptophan degradation is reflected in the increase in plasma metabolitesof kynurenine pathway. Hemodialaysis is one of therapeutic approachesthat significantly reduce all plasma kynurenine metabolites in uremicpatients. In spite of haemodialaysis, plasma concentration of kynurenine,kynurenic acid, 3-hydroxykynurenine, anthranilic acid, xanthurenicacid and quinolinic acid were still elevated in uremic patients in comparisonwith healthy volunteers. These data shows significant disturbances inkynurenine metabolism in uremic patients. Accumulation of thesesubstances in uremic blood is capable to account for certain uremicsymptoms.