؊1 cut-points, diagnostic efficiencies of cystatin C (89% and 92%) were better than those of the other variables (79%-82% and 85%-86%, respectively; P ‫؍‬ 0.01).

Cystatin C (Cys C) is a cysteine protease inhibitor produced at a constant rate by nucleated cells, filtered through the glomerular membrane and reabsorbed by kidney tubular cells. Aim of this cross-sectional and longitudinal study was to assess serum Cys C and creatinine (Crea) concentrations in thyroid dysfunction. One hundred and eighty-one patients, 26 with untreated non-toxic nodular goiter, 58 with hyperthyroidism, 31 on L-T4 suppressive therapy for non-toxic nodular goiter, 35 with short-term hypothyroidism after L-T4 withdrawal to perform whole body scan for thyroid cancer, 11 with long-term hypothyroidism due to chronic autoimmune thyroiditis and 20 patients with mild hypothyroidism were enrolled in the study. Fifty-seven age- and sex-matched normal subjects served as controls. Serum Cys C, Crea, free T4 (FT4), FT3 and TSH were assessed. Thirty hyperthyroid patients and 35 short-term hypothyroid patients were followed prospectively until euthyroidism was reached by methimazole or L-T4 therapy. The cross-sectional study showed that mean serum Crea concentrations were significantly reduced in overt hyperthyroid or subclinical hyperthyroid patients, while it was increased in overt hypothyroid patients, but not in mild hypothyroidism. Conversely, serum Cys C levels were significantly increased in overt hyperthyroid patients compared to controls (p<0.05), and significantly decreased in short-term, long-term and mild hypothyroids (p<0.05, p<0.05, p<0.01, respectively). However, 36 (62%) hyperthyroid patients and 50 (76%) hypothyroid patients had normal serum Cys C values. In the prospective study, restoration of euthyroidism by either methimazole or L-T4 therapy was associated with normalization of mean serum Cys C concentrations. In conclusion, thyroid dysfunction affects serum Cys C concentration, possibly influencing the production rate of the protein. However, the observation that hyper- or hypothyroid patients have normal serum Cys C levels limits its use as a marker of peripheral thyroid hormone effect.

Haptoglobin (Hp) is a glycoprotein involved in the acute phase response to inflammation. Our previous findings indicate that Hp mRNA and protein are present in the adipose tissue of rodents and that Hp gene expression is up-regulated in obese models. The aim of the present study was to establish whether Hp could be considered a marker of obesity in humans. In 312 subjects, serum Hp was correlated directly with body mass index (BMI), leptin, C-reactive protein (CRP), and age. In a multivariate stepwise regression analysis, BMI and CRP were independent determinants of serum Hp in females, with BMI having the strongest effect. CRP and age were independent determinants of serum Hp in males, although explaining only a modest percentage of the total variability. Serum Hp was positively associated with body fat, as assessed by dual-energy x-ray absorptiometry, both in female and in male groups. The level of significance improved when serum Hp was analyzed against fat mass adjusted for lean mass. Finally, Northern and Western blot analyses performed in biopsies of sc abdominal fat from 20 obese individuals showed the presence of Hp mRNA and protein in the human adipose tissue. In conclusion, serum Hp constitutes a novel marker of adiposity in humans, and the adipose tissue likely contributes to determine its levels.

Increase in adipose mass results in obesity and modulation of several factors in white adipose tissue (WAT). Two important examples are tumor necrosis factor alpha (TNFalpha) and leptin, both of which are upregulated in adipose tissue in obesity. In order to isolate genes differentially expressed in the WAT of genetically obese db/db mice compared to their lean littermates, we performed RNA fingerprinting and identified haptoglobin (Hp), which is significantly upregulated in the obese animals. Hp is a glycoprotein induced by a number of cytokines, LPS (Lipopolysaccharide), and more generally by inflammation. A significant upregulation of WAT Hp expression was also evident in several experimental obese models including the yellow agouti (/) A(y), ob/ob and goldthioglucose-treated mice (10-, 8-, and 7-fold, respectively). To identify the potential signals for an increase in Hp expression in obesity, we examined leptin and TNFalpha in vivo. Wild type animals treated with recombinant leptin did not show any alteration in WAT Hp expression compared to controls that were food restricted to the level of intake of the treated animals. On the other hand, Hp expression was induced in mice transgenically expressing TNFalpha in adipose tissue. Finally, a significant downregulation of WAT Hp mRNA was observed in ob/ob mice deficient in TNFalpha function, when compared to the ob/ob controls. These results demonstrate that haptoglobin expression in WAT is increased in obesity in rodents and TNFalpha is an important signal for this regulation.

C-reactive protein (CRP) levels have not been routinely used to diagnose thyroid disease, although many thyroid conditions involve inflammation. This study was intended to determine whether CRP levels could differentiate between inflammatory and noninflammatory thyroid conditions, especially between type II inflammatory amiodarone-induced thyrotoxicosis (AIT) and type I iodine-induced AIT. Serum high-sensitivity CRP levels were measured in 100 euthyroid controls (7 taking amiodarone) and 353 patients with one of the following thyroid conditions: AIT, subacute thyroiditis, toxic diffuse goiter, nodular goiter, Hashimoto's thyroiditis, shortterm hypothyroidism, or postpartum thyroiditis. No patients with nontoxic multinodular goiter (n = 34), toxic nodular goiter (n = 23), or toxic diffuse goiter, either untreated (n = 49) or euthyroid while taking methimazole (n = 33), had positive CRP levels (>10 mg/L). The occurrence of positive CRP levels among patients with Hashimoto's thyroiditis (n = 35), short-term hypothyroidism (n = 38), and postpartum thyroiditis (n = 70) did not differ significantly from controls. The occurrence of positive CRP values did not differ significantly between patients with type I and type II AIT and controls. Six of 7 patients (86%) with untreated subacute thyroiditis had positive CRP levels (p < 0.00001). These results indicate that there is only a limited role for measurement of CRP levels in the diagnosis of thyroid diseases other than subacute thyroiditis.

To verify whether cystatin C may be of some use as a renal function marker immediately after orthotopic liver transplantation (OLT), we compared serum cystatin C (S Cyst ), serum creatinine (S cr ), and creatinine clearance (C cr ) levels with the glomerular filtration rate (GFR). On postoperative days 1, 3, 5, and 7, S Cyst and S cr was measured in simultaneously drawn blood samples, whereas C cr was calculated using a complete 24-hour urine collection. The GFR was determined on the same days by means of iohexol plasma clearance (I-GFR). The correlation between 1/S Cyst and I-GFR was stronger than that of 1/S cr or C cr (P < 0.01). In the case of moderate reductions in I-GFR (80-60 mL/minute/1.73 m 2 ), S cr remained within the normal range, whereas the increase in S cyst was beyond its upper limit; for I-GFR reductions to lower levels (59-40 mL/minute/1.73 m 2 ), S cr increased slightly, whereas S cyst was twice its upper normal limit. When we isolated all of the I-GFR values on days 3, 5, and 7 that were >30% lower than that recorded on the first postoperative day, S Cyst (P < 0.0001) and S cr (P < 0.01) levels were increased, whereas C cr remained unchanged (P ‫؍‬ 0.09). Receiver operating characteristic (ROC) area-under-the-curve analysis showed that the diagnostic accuracy of S cyst was better than that of S cr and C cr . S cyst levels of 1.4, 1.7, and 2.2 mg/L respectively predicted I-GFR levels of 80, 60, and 40 mL/minute/1.73 m 2 . In conclusion, cystatin C is a reliable marker of renal function during the immediate post-OLT period, especially when the goal is to identify moderate changes in GFR. It has been widely demonstrated that acute renal failure can severely affect the postoperative course of a complex procedure such as orthotopic liver transplantation (OLT). 1,2 As renal function can be threatened for different reasons in the period immediately following OLT (i.e., hemodynamic disturbances, drug nephrotoxicity, acute surgical or infectious complications), it is very important for clinicians to have access to sensitive and reliable markers that can promptly identify renal dysfunction from its initial stage in order to allow them to adopt the necessary preventive and supportive measures for avoiding or containing the development of renal damage.Although commonly used, the measurement of serum creatinine (S cr ) and the calculation of creatinine clearance (C cr ) are not very reliable in cirrhotic patients undergoing OLT because some of the peculiarities of the liver disease (reduced muscle mass, decreased creatinine biosynthesis, high blood bilirubin levels) can lead to false results. [3][4][5] Furthermore, it has been reported that making routine S cr measurements is an insensitive way of assessing renal function in patients adminis-

No abstract

Renal disease patients often exhibit alterations in the lipid profile which may become an important risk of accelerated atherosclerosis and contribute to disease progression. Among such alterations, increased levels of lipoprotein(a) [Lp(a)] are common and may be related, in part, to the degree of proteinuria. Omega-3 polyunsaturated fatty acids (ω-3 FA) have been reported to decrease Lp(a) concentrations in nonrenal subjects. In addition, they have recently been shown to reduce proteinuria in patients with chronic glomerular disease. We therefore tested the hypothesis that ω-3 FA treatment in patients with chronic glomerular disease may reduce Lp(a) concentrations. Eight patients (2 with membranous glomerulonephritis, 6 with focal glomerular sclerosis) were submitted to a total of 13 six-week courses of treatment with ω-3 FA, at a dose of 3 g/day with a triglyceride preparation (n = 4) and of 7.7 g/day with an ethyl-ester preparation (n = 9). Both treatments significantly increased the proportions of ω-3 to ω-6 FA in total serum lipids, documenting compliance to treatment. Both treatments were also effective in decreasing serum thromboxane (from mean 490 ± (SEM) 70 to 325 ± 49 ng/ml, p < 0.05, in the high-dose group) and prolonging the bleeding time (from 5.8 ± 0.4 to 7.7 ± 0.5 min, p < 0.05, in the high-dose group), thus documenting the biological efficacy of treatment. However, despite a significant reduction in serum triglyceride levels (from 137 ± 20 to 104 ± 19 mg/dl in the high-dose group), Lp(a) concentrations did not change (292 ± 120 U/l before, 315 ± 130 U/l after the high-dose therapy). Treatment-related changes in proteinuria (from 2.9 ± 0.5 to 2.1 ± 0.7 g/24 h) were not related at all to changes in Lp(a) levels. We conclude that ω-3 FA do not decrease Lp(a) concentrations in renal patients with chronic glomerular diseases and that Lp(a) levels are unlikely to be related to the degree of proteinuria within the short-term modifications induced by ω-3 FA.