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 >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.

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.

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.

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Objective To evaluate the importance of adiponectin and insulin resistance in early-and late-onset pre-eclampsia.Design A nested case-control study in 72 pregnant women who participated in the first-trimester Down-syndrome-screening programme and who delivered at our hospital.Setting University Hospital, Department of Obstetrics and Gynecology.Population Pregnant women: 36 women with pre-eclampsia of which 20 late onset and 16 early onset were compared with 36 uncomplicated pregnancies who delivered at term.Methods In all the women, insulin resistance was calculated by the homeostasis model assessment ratio (HOMA-IR) and plasma adiponectin was determined using an enzyme-linked immunosorbent assay.Main outcome measures Insulin resistance and adiponectin concentration.Results First-trimester plasma adiponectin mean levels in the whole pre-eclampsia group were significantly lower than that in the control group (8.4 ± 3.3 versus 14.8 ± 4.6 microgram/ml; P < 0.001), whereas first-trimester mean HOMA-IR values were significantly higher in the pre-eclampsia group than that in the control group (2.0 ± 1.1 versus 1.0 ± 0.4; P = 0.01). Plasma adiponectin concentrations at delivery in the pre-eclampsia group were significantly higher than that in the control group (9.2 ± 3.7 versus 7.8 ± 2.6 microgram/ml; P = 0.04). First-trimester plasma adiponectin mean concentrations in the late-onset subgroup were significantly lower compared with the concentrations in early-onset subgroup (6.2 ± 1.4 microgram/ml versus 11.1 ± 3.2 microgram/ ml; P < 0.001), and there was a significant difference in adiponectin plasma values only between women in the late-onset pre-eclampsia group versus those in the control group (P < 0.001). First-trimester mean HOMA-IR values were significantly higher in the late-onset subgroup compared with that of the early-onset subgroup (2.5 ± 1.3 versus 1.3 ± 0.3; P = 0.02), and there was a significant difference only between the control group versus the late-onset subgroup (P = 0.001).Conclusions First-trimester adiponectin and HOMA-IR values seem to select two completely different populations: early-and late-onset pre-eclampsia, which might suggest a different pathogenesis.

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.

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.

Elevated fibrinogen is independently associated with LV concentric hypertrophy and systolic dysfunction in ESRD patients. These relationships may contribute to the negative prognostic impact of elevated fibrinogen levels in ESRD.