OBJECTIVETo investigate the association between aortic stiffness and incident albuminuria and the decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSWe investigated 461 Japanese type 2 diabetic patients, comprising 199 women and 262 men, with a mean age of 59 ± 11 years. Patients were divided into two groups according to the median value of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness. The end point was defined as the transition from normo- to microalbuminuria or micro- to macroalbuminuria. The Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% CI. The correlation between cf-PWV and rate of change in eGFR was also determined by linear regression analysis.RESULTSThe baseline mean (± SD) cf-PWV was 9.6 ± 2.4 m/s. During a median follow-up period of 5.9 years (range 0.3–8.6), progression of albuminuria was observed in 85 patients. The 5-year cumulative incidence of the end point in patients with cf-PWV below and above the median was 8.5 and 19.4%, respectively (P = 0.002, log-rank test). cf-PWV was significantly associated with incident albuminuria (HR 1.23, 95% CI 1.13–1.33, P < 0.001) by multivariate Cox regression analysis. A significant association between cf-PWV and annual change in eGFR was also suggested by multiple linear regression analysis (standardized estimate −0.095, P = 0.031).CONCLUSIONSAortic stiffness is associated with incident albuminuria and the rate of decline in glomerular filtration rate in type 2 diabetic patients.

Higher plasma levels of ADMA may be a novel and potent predictor of the progression of nephropathy in adult Japanese type 2 diabetic patients.

Aims/hypothesis: Anaemia has been suggested to be an independent risk factor for subsequent progression of advanced diabetic nephropathy; however, the relationship between haemoglobin levels and progression of nephropathy in patients without clinical albuminuria is unknown. Methods: We conducted this prospective hospital-based cohort study of 464 type 2 diabetic patients (149 women and 315 men, 55±13 [mean±SD] years of age) with serum creatinine <177 μmol/l (2.00 mg/dl) and urinary albumin : creatinine ratio <300 mg/g creatinine. GFR was estimated using the equation formulated by the Modification of Diet in Renal Disease Study group, refitted for Japanese individuals. Most patients had haemoglobin concentrations in the normal range (144±15 g/l), only modest renal impairment (GFR: 74.8±14.5 ml min −1 1.73 m −2 ), and normal urinary albumin levels (81.5/18.5% with normo-/microalbuminuria). The primary outcome measurement was the rate of change in GFR determined by regression analysis with GFR as a function of time. Patients were followed up for a mean observation period of 5.0±0.9 (range: 2.5 to 6.2) years. Results: Univariate and multiple regression analyses yielded a significant association between the rate of change in GFR and baseline haemoglobin concentration. After adjusting for covariates, the rate of decline in GFR was significantly greater in patients in the lowest haemoglobin quartile (−3.27 ml min −1 1.73 m −2 year −1 ) than in the third (−2.71 ml min −1 1.73 m −2 year −1 , p=0.024) and highest quartiles (−2.78 ml min −1 1.73 m −2 year −1 , p=0.046). Conclusions/interpretation: Lower haemoglobin concentrations in type 2 diabetic patients without clinical albuminuria may be a significant predictor of subsequent decline in GFR.

Aims/Introduction: Recent observational studies suggest elevated levels of bilirubin, an endogenous anti-oxidant, might protect against kidney disease. We carried out an observational cohort study to assess whether higher baseline levels of bilirubin, within normal range, could predict the rate of development and progression of diabetic nephropathy in patients with type 2 diabetes. Materials and Methods: Japanese type 2 diabetic patients with normo-or microalbuminuria and normal serum bilirubin (<1.2 mg/dL) were recruited from a single center, and categorized according to baseline serum bilirubin levels. Two independent end-points were specified: development or progression of diabetic nephropathy, based on transition to a more advanced stage of albuminuria (albuminuria cohort), and the rate of change in estimated glomerular filtration rate (eGFR cohort). Results: Albuminuria and eGFR cohorts were constructed consisting of 1,915 patients and 1,898 patients, respectively, with 1,738 patients overlapping. Mean follow up was 4.4 and 5.4 years for the two cohorts, respectively. Within the albuminuria cohort, 132 (9%) of 1,418 patients with normoalbuminuria developed microalbuminuria, and 56 (11%) of 497 patients with microalbuminuria developed macroalbuminuria. Higher baseline bilirubin levels were associated with significantly lower risk of progression from microalbuminuria to macroalbuminuria in both the univariate and multivariate analyses. In normoalbuminuric patients, an inverse association was found when restricted to a subgroup with elevated hemoglobin A1c levels. There was no relationship between bilirubin levels and the rate of change in eGFR. Conclusions: Higher serum bilirubin levels, within normal range, might be predictive of a lower risk of progression of nephropathy in type 2 diabetic patients.

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