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 m²) 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.

Chronic kidney disease is a growing public health problem, as its prevalence and incidence have almost doubled over the last three decades. Chronic kidney disease is defined as the presence of an estimated glomerular filtration rate < 60 ml/min/1.73 m2 and/or proteinuria ≥ 0.150 g/24 h. It has been demonstrated that both proteinuria and reduction in estimated glomerular filtration rate can predict the development of fatal and non-fatal cardiovascular events, regardless of traditional cardiovascular risk factors, namely blood pressure, smoking habit, cholesterol, age, gender. This relationship is found in the general population, high-risk cohorts and in patients referred to Nephrologists (tertiary care). The accuracy by which proteinuria or estimated glomerular filtration rate can predict these events, exceeds that obtained by the combination of all the other traditional risk factors. These important findings have led to chronic kidney disease being considered as a cardiovascular risk equivalent. Although this needs further investigation, a great effort has been made to reduce the cardiovascular risk in chronic kidney disease patients. Indeed, many clinical trials have been carried-out testing the effect of antihypertensive, proteinuria-lowering, lipid-lowering and hypoglycemic agents on cardiovascular risk protection. All these trials reduced, but did not eliminate, the overall cardiovascular risk. Future studies should be undertaken to identify high cardiovascular risk patients and novel therapeutic targets for cardiovascular protection in chronic kidney disease patients.