Urinary neutrophil gelatinase-associated lipocalin and progression of diabetic nephropathy in type 1 diabetic patients in a four-year follow-up study.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), a marker of renal tubular damage, predicts progression in non-diabetic chronic kidney. We evaluated urinary (u)-NGAL as a predictor of progression in diabetic nephropathy in type 1 diabetic (T1D) patients. METHODS: As a substudy of a 4-year randomized, intervention study evaluating low-protein diet in T1D patients with diabetic nephropathy, 78 patients were studied with yearly measurements of u-NGAL (ELISA, BioPorto). OUTCOME: Decline in glomerular filtration rate (GFR) ((51)Cr-EDTA), and end-stage renal disease (ESRD) or death. RESULTS: Mean age 40.7 (8.2) years and 50 men. 13 patients developed ESRD or died. Baseline GFR (mean, SD): 68 (31) ml/min/1.73 m(2). Baseline u-NGAL [geometric mean (95% CI)] and GFR were 15.6 ng/24 h (11.8-20.7) and 68 (31) ml/min/1.73 m(2). During follow-up, an increase in u-NGAL [geometric mean (95% CI)] of 15%/year (4-27) and a decline in GFR of 3.7 (3.0) ml/min/year were observed. Baseline u-NGAL was not associated with the decline in GFR. Elevated u-NGAL at baseline (log-transformed) predicted death and ESRD (HR 3.8, 95% CI 1.04-14.0), however not after adjustment for known progression promoters (HR 2.0, p = 0.6). CONCLUSION: Elevated u-NGAL was not related to decline in GFR during a 4-year follow-up. Elevated u-NGAL was associated with the development of ESRD and death, but not after adjustment.

Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study.

OBJECTIVE: To evaluate baseline predictors for the development of persistent microalbuminuria and macroalbuminuria prospectively in patients with type 1 diabetes. DESIGN: Prospective observational study of an inception cohort. SETTING: Outpatient diabetic clinic in a tertiary referral centre, Gentofte, Denmark. PARTICIPANTS: 286 patients (216 adults) newly diagnosed with type 1 diabetes consecutively admitted to the clinic between 1 September 1979 and 31 August 1984. MAIN OUTCOME MEASURES: Persistent microalbuminuria and persistent macroalbuminuria. RESULTS: During the median follow up of 18.0 years (range 1.0-21.5 years), total of 4706 patient years of follow up, 79 of 277 (29%) patients developed persistent microalbuminuria. 27 of 79 progressed further to persistent macroalbuminuria. The cumulative incidence of persistent microalbuminuria and persistent macroalbuminuria was 33.6% (95% confidence interval 27.2% to 40.0%) and 14.6% (8.9% to 20.3%), respectively. Significant predictors for the development of persistent microalbuminuria were a 10-fold increase in urinary albumin excretion rate (relative risk 3.78, 1.57 to 9.13), being male (2.41, 1.43 to 4.06), a 10 mm Hg increase in mean arterial blood pressure (1.38, 1.20 to 1.57), a 1% increase in haemoglobin A1c (1.18, 1.04 to 1.32), and a 1 cm increase in height (0.96, 0.95 to 0.98). 28 patients with microalbuminuria (35%) regressed to normoalbuminuria either transiently (n = 15) or permanently (n = 13). CONCLUSIONS: Around one third of patients newly diagnosed with type 1 diabetes develop persistent microalbuminuria within the first 20 years of diabetes. Several potentially modifiable risk factors predict the development of persistent microalbuminaria and persistent macroalbuminuria.