Intensive lipid-lowering therapy ameliorates novel calcification markers and GSM score in patients with carotid stenosis.

OBJECTIVES/DESIGN: Carotid plaque echogenicity quantified by the Gray-Scale Median (GSM) score has been associated with plaque vulnerability. The aim of this study was to assess whether intensive lipid-lowering treatment with atorvastatin in patients with carotid artery stenosis ameliorates novel vascular calcification inhibitors, such as osteopontin (OPN) and osteoprotegerin (OPG), and improves GSM score. METHODS: Ninety-seven patients with carotid stenosis (>40%), but without indication for intervention, were treated for 6 months with atorvastatin (10mg-80mg) to target LDL<100mg/dl. Fifty-two age-and sex-matched healthy individuals served as the control group. Blood samples and GSM were obtained at the beginning and after 6 months. RESULTS: Systolic blood pressure, hsCRP, fibrinogen, OPN and OPG levels differed significantly between patients with carotid stenosis and healthy controls at baseline (p<0.05). Atorvastatin treatment improved lipid profile and significantly reduced hsCRP (p=0.002), WBC count (p=0.041), OPN (p<0.001) and OPG levels (p<0.001). GSM score increased considerably after atorvastatin therapy (from 58.33+/-24.38 to 79.33+/-22.3; p<0.001) and that effect appeared related to OPN (p=0.001), OPG (p=0.013) and LDL (p=0.01) reduction. CONCLUSIONS: In patients with carotid stenosis, intensive lipid-lowering therapy with statins attenuates serum OPN and OPG levels and enhances carotid plaque echogenicity, outlining their beneficial effects on plaque stability.

Single kidney function: early and late changes in urate transport after nephrectomy.

Renal urate transport was studied by means of pyrazinamide (PZA) and probenecid (PB): (a) before and at 2, 6, 24 weeks (24 patients), (b) 1 to 30 years after uninephrectomy in 27 and 12 patients with Ccr greater than 80 and 30 to 70 ml/min, respectively. Uninephrectomy was followed by important tubular urate transport modifications during at least two weeks, which lead to a marked uricosuria as indicated by significant increase in FEur (mean value +/- SD, 0.228 +/- 0.059 vs. 0.097 +/- 0.014 and 0.099 +/- 0.019 in normals and chronically diseased solitary kidneys). Reduced response to PZA and PB suggests a diminished reabsorptive capacity for urate mainly at the presecretory site which persisted after FENa normalization. Tubular compensations were presumably complete at six weeks, since pattern of urate transport returned to normal with an almost complete reabsorption of filtered urate load (99%) and a percentage of postsecretory reabsorption (80%) very close to those seen in normal subjects with a pair of kidneys. The adjustment in urate excretion in solitary kidneys was achieved by a significant increase of secreted urate as compared with 50% of pre-uninephrectomy values. Thus, increased urate secretion by the remaining intact organ is sufficient to maintain urate balance with a normal serum level.