Renal vascular remodeling processes in young ADPKD patients with normal renal function: a cross-sectional study

PABLO J AZURMENDI; ADRIANA R FRAGA; FELICITA M GAL¨¢N; CAROL KOTLIAR; ELVIRA E ARRIZURIETA; MARTA G VALDEZ; PEDRO J FORCADA; JOS¨¦ SANTELHA STEFAN; RODOLFO S MART¨ªN

Montreal, Canad¨¢

Congreso; ISN Forefronts Symposium on ADPKD; 2008

Int Soc Nephrology

Background: We have previously described that minimal increased albuminuria (urine albumin/urine creatinine ACR>6.8 mg/g) is associated with increased monocyte-chemoattractant protein 1 (MCP-1) in a young ADPKD population with normal renal function, suggesting early kidney remodeling. The aim of this study was to evaluate whether these renal markers are simultaneously associated with early vascular and inflammatory/fibrotic alterations. Methodology: Forty-eight ADPKD patients (mean age 25 ¡À 1 y) with normal renal function (108 ¡À 3 ml/min/1.73m2) by MDRD formula and without overt proteinuria and 21 matched healthy controls (mean age 26 ¡À 1 y) were studied.  Plasma MCP-1 and transforming growth factor-b1 (TGF-b1) were determined by ELISA as systemic inflammatory and fibrotic markers, respectively. In thirty patients and 14 controls carotid intima-media thickness (IMT), endothelium-dependent vascular relaxation (EDVR) and aortic pulse-wave velocity (Ao-PWV) were measured by ultrasound established methods. Results: IMT (mm) was higher in ADPKD than controls (0.51 ¡À 0.08 vs 0.44 ¡À 0.07), even when a normotensive patient subset was analyzed (0.52 ¡À 0.06, p < 0.005). Patients with ACR > 6.8 mg/g (n = 16) showed higher IMT when compared with patients with ACR ¡Ü 6.8 mg/g (n = 14; 0.56 ¡À 0.07 vs. 0.47 ¡À 0.06, respectively, p<0.005), even in the normotensive patient subset (0.55 ¡À 0.05 and 0.49 ¡À 0.05, respectively, p < 0.005). Plasma MCP-1 (pg/ml) and TGF-b1 (ng/ml) were not different in ADPKD (84.2 ¡À 6.3 and 46 ¡À 0.4, respectively) from controls (67.4 ¡À 0.6 and 5.5 ¡À 06, respectively). No differences were found in EDVR and Ao-PWV. ADPKD patients with ACR ¡Ü 6.8 mg/g Cr showed no differences with controls in both urine MCP-1 excretion (77.7 ¡À 13.9 vs. 57.8 ¡À 6.3 ng/g Cr, respectively) and IMT. Conclusion: Vascular alterations were present in early stages of ADPKD, associated with high urine albumin and MCP-1 excretion, but not with systemic inflammatory/fibrosis or hypertension. The results suggest that the vascular phenotype in ADPKD could be a manifestation of the disease independent of the systemic inflammatory/fibrosis process and that urine albumin could be a useful pathogenic marker.