Early renal and vascular changes in ADPKD patients with low-grade albumin excretion and normal renal function

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) shows an increase in both urine monocyte chemoattractant protein-1 (MCP-1) and carotid intima-media thickness (CIMT) before changes in serum creatinine concentration. Although microalbuminuria is an index of disease progression, data on whether renal alterations and vascular remodelling are already present at normal or minimally increased levels of urine albumin excretion in early stages of the disease are lacking. Forty-eight ADPKD patients (24.8 +/- 0.8 years) with normal renal function (MDRD 108.1 +/- 3.1 ml/min) and 21 age-matched controls were studied in a cross-sectional study. The urine albumin/creatinine ratio (UACR) above the upper range of controls (6.8 mg/g) was taken as the predictor of renal alterations and vascular remodelling. Urine MCP-1, MCP-1 fractional excretion (FE(MCP-1)), endothelial-dependent vascular relaxation (EDVR), aortic pulse-wave velocity (Ao-PWV) and CIMT were chosen as biological markers. No differences between ADPKD with UACR <or=6.8 mg/g and controls were observed in urine MCP-1 (77.7 +/- 13.9 versus 57.8 +/- 6.3 ng/g), FE(MCP-1) (91 +/- 19 versus 74 +/- 8%) and CIMT (0.47 +/- 0.06 versus 0.44 +/- 0.07 mm), respectively. Conversely, ADPKD with UACR >6.8 mg/g showed values that were different from the two other groups. In addition, patients with UACR >6.8 and <20 mg/g showed greater values for urine MCP-1, FE(MCP-1) and CIMT (131.8 +/- 21.7 ng/g, 159 +/- 31% and 0.55 +/- 0.05 mm, respectively), as compared with patients with UACR <or=6.8 mg/g. The same pattern was found in a subset of normotensive ADPKD patients. No differences were found in EDVR and Ao-PWV. In young ADPKD patients, normal levels of UACR suggest that renal interstitium is comparable to that in healthy subjects and indicate an absence of subtle atherosclerotic changes in the carotid arteries. Likewise, early renal and vascular changes may be present at UACR below the levels defined as microalbuminuria.