Low preoperative hepcidin concentration as a risk factor for mortality after cardiac surgery: a pilot study.

OBJECTIVE: Hepcidin regulates iron absorption and recycling and is central to host defense, protection from reactive iron species, and a biomarker of iron-related pathophysiology. We assessed the value of hepcidin measured preoperatively for the prediction of in-hospital mortality and renal outcomes. METHODS: We studied 100 adult patients undergoing cardiac surgery in the control arm of a randomized, controlled trial. Plasma and urine were sampled before induction of anesthesia, and hepcidin-25 was quantified by competitive enzyme-linked immunoassay. Renal outcomes were acute kidney injury defined by risk, injury, failure, loss of function, end-stage renal disease (RIFLE) classification and need for renal replacement therapy. Variables with the potential to influence hepcidin expression were investigated. RESULTS: Low preoperative hepcidin concentration in urine (median, 15.3 ng/mL; 25-75 percentiles, 0-129.1) and plasma (median, 49.2 ng/mL; 25th-75th percentile, 0-52.2) predicted mortality (area under the curve-receiver operating characteristic [AUC-ROC] for urine hepcidin, 0.89; 95% confidence interval, 0.73-0.99; cutoff, 130 ng/mL; sensitivity, 73%; specificity, 100%; and AUC-ROC for plasma hepcidin, 0.90; 95% confidence interval, 0.80-0.99; cutoff, 55 ng/mL; sensitivity, 83%; specificity, 100%). Survivors had median preoperative hepcidin concentrations of 325.3 ng/mL (25th-75th percentile, 120-770.1 ng/mL) in urine and 113.1 ng/mL (25th-75th percentile, 77.7-203.1 ng/mL) in plasma. Preoperative serum creatinine did not predict mortality (AUC-ROC, 0.50; 95% confidence interval, 0.10-0.94). Furthermore, preoperative urine, plasma hepcidin, and serum creatinine did not distinguish patients requiring postoperative renal replacement therapy from those without (urine: AUC-ROC, 0.62; 95% confidence interval, 0.38-0.86; plasma: AUC-ROC, 0.63; 95% confidence interval, 0.34-0.91; serum creatinine: AUC-ROC, 0.61; 95% confidence interval, 0.22-0.99). Preoperative renal function and hemoglobin did not correlate with hepcidin indices whereas plasma markers of inflammation did. CONCLUSIONS: Low preoperative hepcidin concentration might be a risk factor for in-hospital mortality. Findings should be validated in larger patient cohorts with a greater number of events.

Resistin serum levels are increased but not correlated with insulin resistance in chronic hemodialysis patients.

BACKGROUND/AIMS: Insulin resistance is a well-known phenomenon in uremia. Resistin, a recently discovered insulin inhibitor secreted by adipocytes, is associated with obesity and insulin resistance in mice. Adiponectin, also secreted by adipocytes, is known to reduce insulin resistance in humans. The aim of the present study was to address the hypothesis that changes in resistin or adiponectin serum levels may relate to body composition and to insulin resistance in patients with end-stage renal disease. METHODS: In a cross-sectional study, 33 non-diabetic patients (24 males and 9 females, mean age 61.5+/-15.8 years) with end-stage renal disease on chronic hemodialysis (treatment duration 41+/-31 months) that lacked signs of infection were enrolled. The control group consisted of 33, matched for age, sex and body mass index (BMI), healthy volunteers (22 males, 11 females, mean age 62.6+/-12.1 years). BMI (kg/m(2)) was calculated from body weight and height. Body fat (%) was measured by means of bioelectrical impedance. Blood samples were taken always in the morning after a 12-hour fasting period before and after the hemodialysis session. Resistin and adiponectin serum concentrations were measured by enzyme immunoassays and insulin by an electrochemiluminescence immunoassay. The post-treatment values were corrected regarding the hemoconcentration. The homeostasis model assessment index (HOMA-R) was calculated as an estimate of insulin resistance from the fasting glucose and insulin serum levels. RESULTS: Pre-treatment resistin serum levels were significantly increased in hemodialysis patients compared to healthy controls (19.2+/-6.2 vs. 3.9+/-1.8 ng/ml; p<0.001). Hemodialysis did not alter resistin levels, as pre- and post-treatment levels were not different when corrected for hemoconcentration (19.2+/-6.2 vs. 18.7+/-5.0 ng/ml; p=0.54). Adiponectin levels were also increased in hemodialysis patients compared to healthy controls (25.4+/-21.5 vs. 10.5+/-5.9 microg/ml; p<0.001). A significant inverse correlation was observed between the serum adiponectin levels before the hemodialysis session on the one hand and the BMI (r=-0.527, p=0.002), the HOMA-R (r=-0.378, p<0.05) and the fasting insulin levels (r=-0.397, p<0.05) on the other. However, no significant correlation was observed between serum resistin levels on the one hand versus HOMA-R index (3.2+/-3.9 mmol.microIU/ml; r=-0.098, p=0.59), insulin levels (13.3+/-14.4 mU/l; r=-0.073, p=0.69), glucose levels (89+/-13 mg/dl; r=-0.049, p=0.78), BMI (25.6+/-3.7 kg/m(2); r=-0.041, p=0.82) and body fat content (26.4+/-8.4%; r=-0.018, p=0.94) on the other hand. CONCLUSION: Resistin serum levels are significantly elevated in non-diabetic patients with end-stage renal disease that are treated by hemodialysis. The hemodialysis procedure does not affect the resistin levels. Along with previous observations in patients with renal insufficiency in the pre-dialysis stage, our findings implicate an important role of the kidney in resistin elimination. However, increased resistin serum levels in hemodialysis patients are not related to reduced insulin sensitivity encountered in uremia.

Impaired balance of type I and type III procollagen mRNA in cultured fibroblasts of patients with incisional hernia.

BACKGROUND: Recent findings of an impaired protein ratio of type I to type III procollagen showed a disturbed collagen metabolism in incisional hernia development. We analyzed the type I and type III procollagen messenger RNA to investigate whether these findings represent the altered extracellular matrix or a primary defect at the transcriptional level. METHODS: We examined cultured skin fibroblasts of patients with incisional or recurrent incisional hernia in comparison with those without any previous incision (control) and those with a skin scar without clinical appearance of a hernia (scar). Immunohistochemical detection of a lowered protein ratio of type I and type III collagen in the hernia skin tissue leads to mRNA expression analysis. The procollagen mRNA and the ratio of type I to type III procollagen mRNA are detected by reverse transcriptase-polymerase chain reaction and Northern blot analysis, the collagens type I and III by Western blot analysis. RESULTS: Reverse transcriptase-polymerase chain reaction revealed an increase of type I procollagen mRNA in the incisional and recurrent hernia (0.90 +/- 0.04 and 1.19 +/- 0.04, respectively) compared with stable scar (0.54 +/- 0.02) or healthy tissue (0.43 +/- 0.01). The obvious rise of type III procollagen mRNA to 4.13 +/- 0.04 for incisional, 6.02 +/- 0.03 for recurrent hernia, 2.29 +/- 0.04 for stable scar, and 1.72 +/- 0.03 for the healthy tissue showed a significantly decreased ratio of type I to type III procollagen mRNA in the hernia patients as compared with the controls (P <.01). By Western blot analysis, an increase of type I and type III collagen protein and a significant rise in the corresponding ratio in the recurrent hernia group were detected. CONCLUSIONS: The altered synthesis of type I and type III collagen in cultured skin fibroblasts suggests a disorder of collagen metabolism, at least in patients with recurrent hernia. Hence, a basically impaired wound healing process is likely to contribute to the unsatisfactory results of incisional hernia repair.