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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.

Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.

Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; =145) or walking exercise (=151); 227 patients (exercise =104; control=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; <0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; =0.001 between groups). The cognitive function score (=0.04) and quality of social interaction score (=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis.

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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.

Aldosterone antagonists reduced proteinuria and blood pressure in adults who had mild to moderate CKD and were treated with ACEi or ARB (or both), but increase hyperkalaemia and gynaecomastia. Whether adding aldosterone antagonists to ACEi or ARB (or both) reduced the risk of major cardiovascular events or ESKD in this population is unknown.