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Featured researches published by Giacomo Nicocia.


Clinical Journal of The American Society of Nephrology | 2009

Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Progression of Chronic Kidney Disease

Davide Bolignano; Antonio Lacquaniti; Giuseppe Coppolino; Valentina Donato; Susanna Campo; Maria Rosaria Fazio; Giacomo Nicocia; Michele Buemi

BACKGROUND AND OBJECTIVES Chronic kidney disease (CKD) has recently assumed epidemic proportion, becoming a troubling emerging cause of morbidity, especially if it progresses to terminal stage (ESRD). The authors aimed to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL), a novel specific biomarker of acute kidney injury, could predict the progression of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Serum and urinary NGAL levels, together with a series of putative progression factors, were evaluated in a cohort of 96 patients (mean age: 57 +/- 16 years) affected by nonterminal CKD (eGFR > or =15 ml/min/1.73 m(2)) of various etiology. Progression of CKD, assessed as doubling of baseline serum creatinine and/or onset of ESRD, was evaluated during follow-up. RESULTS At baseline, both serum and urinary NGAL were inversely, independently, and closely related to eGFR. After a median follow-up of 18.5 mo (range 1.01 to 20), 31 patients (32%) reached the composite endpoint. At baseline, these patients were significantly older and showed increased serum creatinine, calcium-phosphate product, C-reactive protein, fibrinogen, daily proteinuria, and NGAL levels, whereas eGFR values were significantly lower. Univariate followed by multivariate Cox proportional hazard regression analysis showed that urinary NGAL and sNGAL predicted CKD progression independently of other potential confounders, including eGFR and age. CONCLUSION In patients with CKD, NGAL closely reflects the entity of renal impairment and represents a strong and independent risk marker for progression of CKD.


Kidney & Blood Pressure Research | 2009

Neutrophil Gelatinase-Associated Lipocalin as an Early Biomarker of Nephropathy in Diabetic Patients

Davide Bolignano; Antonio Lacquaniti; Giuseppe Coppolino; Valentina Donato; Maria Rosaria Fazio; Giacomo Nicocia; Michele Buemi

Background/Aims: Renal tubulointerstitium plays an important role in the development and progression of diabetic nephropathy. Methods: With the present study, we aimed at evaluating the levels of neutrophil gelatinase-associated lipocalin (NGAL), a tubular stress protein, in serum (sNGAL) and urine (uNGAL) from a cohort of 56 patients with type 2 diabetes mellitus categorized into three groups (normoalbuminuria, microalbuminuria and diabetic nephropathy). Results: All groups showed increased NGAL values with respect to controls; interestingly, increased NGAL levels were already found in diabetic patients without early signs of glomerular damage (normoalbuminuric). Both sNGAL and uNGAL increased in parallel with the severity of renal disease, reaching higher levels in patients with manifest diabetic nephropathy. The assessment of Pearson coefficient evidenced significant relationships between sNGAL and, respectively, uNGAL, serum creatinine and GFR (inversely) and between uNGAL and, respectively, serum creatinine, proteinuria, albuminuria, serum albumin and GFR (both inversely). Conclusions: NGAL might play an important role in the pathophysiology of renal adaptation to diabetes, probably as a defensive mechanism aiming to mitigate tubular suffering. Furthermore, NGAL measurement might become a useful and noninvasive tool for the evaluation of renal involvement in diabetic patients as well as for the early diagnosis of incipient nephropathy.


American Journal of Nephrology | 2007

Neutrophil Gelatinase-Associated Lipocalin in Patients with Autosomal-Dominant Polycystic Kidney Disease

Davide Bolignano; Giuseppe Coppolino; Susanna Campo; Carmela Aloisi; Giacomo Nicocia; Nicola Frisina; Michele Buemi

It is known that many tubular proteins are involved in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD), which causes 8–10% of the cases of end-stage renal disease (ESRD) worldwide. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein expressed on tubular cells of which the production is markedly increased in response to harmful stimuli such as ischemia or toxicity. In the present study, serum and urinary NGAL levels were evaluated in 26 ADPKD subjects. Both levels were significantly higher in patients than in controls (sNGAL 174 ± 52 vs. 50 ± 27 ng/ml, p < 0.05; uNGAL 119 ± 42 vs. 7 ± 6 ng/ml, p < 0.005) and a close correlation was also found between these parameters and the residual renal function (sNGAL/GFR: r = –0.8, p = 0.006; sNGAL/Creatinine: r = 0.9, p = 0.007; uNGAL/GFR: r = –0.49, p < 0.05; uNGAL/Creatinine: r = 0.84, p < 0.001). Patients were further divided into two groups according to the cystic development assessed with echotomography; subjects with higher cystic growth (HCG) presented higher sNGAL and uNGAL levels with respect to others (sNGAL: 242 ± 89 vs. 88 ± 34 ng/ml, p < 0.05; uNGAL: 158 ± 45 vs. 73 ± 27 ng/ml, p < 0.05). The strict correlation between NGAL levels and residual renal function is perfectly in accord with recent studies on patients with other ESRD-associated diseases. We can hypothesize that tubular cells produce big quantities of NGAL as a consequence of increased apoptosis following chronic damage or as a compensatory response, similar to that observed in acute stress conditions (ischemia, toxicity ...). Finally, our last finding that patients with HCG showed higher levels of NGAL suggests that this protein could be also involved in the cyst growth process, as previously reported about epithelial and tumoral expansion.


Rejuvenation Research | 2009

Increased Plasma Neutrophil Gelatinase-Associated Lipocalin Levels Predict Mortality in Elderly Patients with Chronic Heart Failure

Davide Bolignano; Giorgio Basile; Pina Parisi; Giuseppe Coppolino; Giacomo Nicocia; Michele Buemi

Chronic congestive heart failure (CHF) is associated with an increase in cytokines and inflammatory markers, particularly in elderly patients in whom chronic inflammation is generally present per se. In the present pilot study, neutrophil gelatinase-associated lipocalin (NGAL), a recently discovered cytokine, was analyzed together with different clinical and laboratory parameters in a small cohort of 46 elderly patients with CHF of various degrees. NGAL levels in the cohort were found to be significantly higher than in healthy age-balanced controls (458.5 [62.5-1212.4] vs. 37.8 [15.9-46.5] ng/mL; p = 0.0001). Furthermore, NGAL values increased in parallel with the clinical severity of CHF (New York Heart Association [NYHA] classification), the highest levels being reached in class IV patients (p = 0.0001). After a 2-year follow up, Kaplan-Meier curves indicated that patients with baseline NGAL > 783 ng/mL (best receiver operating characteristic [ROC]-derived cut-off value) had a significantly higher mortality (p = 0.001; log-rank test) and 4.08 hazards ratio (95% confidence interval [CI], 1.29-12.96) for death than the other subjects considered. Although preliminary, our findings suggest that NGAL plays a pivotal role in the systemic adaptation to chronic heart failure in elderly patients. Moreover, they indicate, for the first time, that measurement of NGAL may be of important prognostic value in the assessment of survival, thus extending the predictive properties of this cytokine beyond the clinical field of renal disease.


Journal of Internal Medicine | 2003

Fibrinogen, mortality and incident cardiovascular complications in end-stage renal failure.

Carmine Zoccali; Francesca Mallamaci; Giovanni Tripepi; Sebastiano Cutrupi; Saverio Parlongo; Lorenzo Malatino; Graziella Bonanno; Francesco Rapisarda; Pasquale Fatuzzo; Giuseppe Seminara; Benedetta Stancanelli; Giacomo Nicocia; Michele Buemi

Abstract. Zoccali C, Mallamaci F, Tripepi G, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Rapisarda F, Fatuzzo P, Seminara G, Stancanelli B, Nicocia G, Buemi M (Institute of Biomedicine, Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Cal; University of Catania; and University of Messina, Italy). Fibrinogen, mortality and incident cardiovascular complications in end‐stage renal failure. J Intern Med 2003; 254: 132–139.


Kidney & Blood Pressure Research | 2008

Pathological and Prognostic Value of Urinary Neutrophil Gelatinase-Associated Lipocalin in Macroproteinuric Patients with Worsening Renal Function

Davide Bolignano; Giuseppe Coppolino; Antonio Lacquaniti; Giacomo Nicocia; Michele Buemi

Background/Aims: Persistent proteinuria is a sign of renal damage caused by several factors, but it is itself a cause of tubular injury leading to chronic renal failure. Neutrophil gelatinase-associated lipocalin (NGAL) is a stress protein released by tubular cells which urinary excretion (uNGAL) increases in response to various stimuli. Methods: In the present study we analyzed uNGAL levels in 23 macroproteinuric patients with membranous glomerulonephritis. Results: In these subjects, uNGAL concentrations were significantly higher than in controls, directly correlated with proteinuria and inversely related to residual renal function. Patients were further categorized into two groups, according to a cut-off baseline uNGAL value of 350 ng/ml and evaluated during a 1-year follow-up period. After 12 months, subjects with higher uNGAL levels showed a significant worsening in baseline renal function and a 3.36 risk ratio of developing a severe decrease in GFR (≧50% of baseline values) compared with others. Conclusions: These findings suggest that NGAL may play a key role in tubular adaptations to persistent macroproteinuria. Furthermore, a new, interesting application of NGAL measurement could be proposed in clinical nephrology as a predictor of worsening renal function in patients affected by chronic kidney disease.


Journal of Immunology | 2002

Mitogen-Activated Protein Kinases and NF-κB Are Involved in TNF-α Responses to Group B Streptococci

Giuseppe Mancuso; Angelina Midiri; Concetta Beninati; Giovanna Piraino; A. Valenti; Giacomo Nicocia; Diana Teti; James A. Cook; Giuseppe Teti

TNF-α is a mediator of lethality in experimental infections by group B streptococcus (GBS), an important human pathogen. Little is known of signal transduction pathways involved in GBS-induced TNF-α production. Here we investigate the role of mitogen-activated protein kinases (MAPKs) and NF-κB in TNF-α production by human monocytes stimulated with GBS or LPS, used as a positive control. Western blot analysis of cell lysates indicates that extracellular signal-regulated kinase 1/2 (ERK 1/2), p38, and c-Jun N-terminal kinase MAPKs, as well as IκBα, became phosphorylated, and hence activated, in both LPS- and GBS-stimulated monocytes. The kinetics of these phosphorylation events, as well as those of TNF-α production, were delayed by 30–60 min in GBS-stimulated, relative to LPS-stimulated, monocytes. Selective inhibitors of ERK 1/2 (PD98059 or U0126), p38 (SB203580), or NF-κB (caffeic acid phenetyl ester (CAPE)) could all significantly reduce TNF-α production, although none of the inhibitors used alone was able to completely prevent TNF-α release. However, this was completely blocked by combinations of the inhibitors, including PD98059-SB203580, PD98059-CAPE, or SB203580-CAPE combinations, in both LPS- and GBS-stimulated monocytes. In conclusion, our data indicate that the simultaneous activation of multiple pathways, including NF-κB, ERK 1/2, and p38 MAPKs, is required to induce maximal TNF-α production. Accordingly, in septic shock caused by either GBS or Gram-negative bacteria, complete inhibition of TNF-α release may require treatment with drugs or drug combinations capable of inhibiting multiple activation pathways.


Nephrology Dialysis Transplantation | 2009

Neutrophil gelatinase-associated lipocalin (NGAL) reflects iron status in haemodialysis patients

Davide Bolignano; Giuseppe Coppolino; Adolfo Romeo; Luciano De Paola; Antoine Buemi; Antonio Lacquaniti; Giacomo Nicocia; Luigi Lombardi; Michele Buemi

BACKGROUND An iron deficiency is often present in haemodialysis (HD) patients; however, although transferrin saturation (TSAT) of <20% and/or serum ferritin of <200 ng/mL should express iron scarcity, in HD patients high ferritin levels could be related to inflammation rather than reflecting optimal iron stores. METHODS The aim of the present study was to evaluate serum levels of neutrophil gelatinase-associated lipocalin (NGAL), a small siderophore-binding protein, in a cohort of 56 chronic HD patients in order to determine its possible relationships with iron status. RESULTS NGAL levels were markedly higher in HD patients than in healthy controls; furthermore, HD patients with TSAT <20% had lower NGAL values than healthy controls, whereas the correction of iron deficiency by means of chronic i.v. iron administration significantly increased NGAL values from baseline. Findings from univariate and multivariate analyses demonstrated that NGAL was a significant predictor of hsCRP, spKT/V and TSAT. In ROC analysis, a NGAL cut-off level of <or=473 ng/mL had a greater sensitivity and specificity than a ferritin level of <200 ng/mL in identifying iron deficiency among HD patients. CONCLUSIONS The findings demonstrated that HD patients have altered NGAL values probably because this protein is involved in the maintenance of iron equilibrium. Finally, NGAL might be proposed as a new tool in the assessment of iron deficiency and in the management of iron therapy for HD patients.


European Journal of Clinical Investigation | 2003

Fibrinogen, inflammation and concentric left ventricular hypertrophy in chronic renal failure

Carmine Zoccali; Frank Benedetto; Francesca Mallamaci; Giovanni Tripepi; Sebastiano Cutrupi; Saverio Parlongo; Lorenzo Malatino; Graziella Bonanno; Francesco Rapisarda; Pasquale Fatuzzo; Giuseppe Seminara; Giacomo Nicocia; Michele Buemi

Background We investigated the relationship between fibrinogen and echocardiographic measurements of left ventricular (LV) geometry and LV function in a group of 192 patients with end stage renal disease (ESRD).


Journal of Investigative Medicine | 2008

Effect of a Single Intravenous Immunoglobulin Infusion on Neutrophil Gelatinase-Associated Lipocalin Levels in Proteinuric Patients With Normal Renal Function

Davide Bolignano; Giuseppe Coppolino; Carmela Aloisi; Adolfo Romeo; Giacomo Nicocia; Michele Buemi

ABSTRACT The aim of the present study was to evaluate levels of neutrophil gelatinase-associated lipocalin (NGAL), a stress protein increased after renal and systemic stimuli, in a cohort of 15 patients with severe proteinuria secondary to idiopathic membranous nephropathy and conserved renal function. Neutrophil gelatinase-associated lipocalin levels and the fractional excretion of this protein were higher in patients than in healthy controls. Furthermore, a close correlation was found between serum NGAL and urinary (uNGAL) (r = 0.81; P < 0.01) and between uNGAL and daily proteinuria (r = 0.44; P < 0.03). One hour after infusion of a single high-dose bolus of intravenous immunoglobulin (0.4 g/kg), a new and promising therapy for several kidney diseases, a marked reduction was found in NGAL levels (serum NGAL 194.1 ± 121 vs 370.1 ± 180.5 ng/mL, P < 0.05; urinary NGAL 153.3 ± 108.6 vs 502.2 ± 293.4 ng/mL, P < 0.03); this was maintained 24 hours after the treatment. The findings made suggest that the NGAL balance is altered in patients with severe proteinuria who have not yet developed overt chronic renal failure, thus confirming the potential use of this protein as an early biomarker of kidney damage preceding the increase in serum creatinine levels. Furthermore, also extra-renal cells (neutrophils, endothelium) may hyper-release NGAL, expressing systemic stress related to severe proteinuria. This would explain the impressive decrease occurring in NGAL values after intravenous immunoglobulin infusion, thus providing further evidence of the antiinflammatory properties of this particular therapeutic approach and indicating the possible value of NGAL measurement in monitoring the efficacy of treatment of renal diseases.

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Carmine Zoccali

National Research Council

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