Exercise Induced Myoglobinuria is Determined by Haptoglobin Polymorphism.

BACKGROUND: In professional soccer players (n = 27), confounders of quantitative myoglobinuria following physical training were assessed in order to improve interpretation of post-exercise myoglobinuria. METHODS: Urine samples were collected in the morning before training sessions, 48 to 72 hours following a game. Urine myoglobin was assayed using immunoturbidimetry. Blood was drawn 48 hours following training session. Creatinine was assayed using a Jaffe method. Creatine kinase (CK) activity was assayed according to the IFCC reference method. Serum myoglobin was assayed using the same assay as the one used for urine. Hp polymorphism was assessed on hemoglobin supplemented serum. Serum Hp concentration was assayed nephelometrically. Training intensity was assessed using a wearable GPS tracking system. Physical load monitoring included the covered total distance, the distance at different speed zones, and the number of sprints/accelerations/decelerations/jumps. Multiple regression analysis was used to detect the determinants of post-exercise myoglobinuria. RESULTS: Myoglobinuria negatively correlated with serum haptoglobin (Hp) concentration. Athletes presented with Hp values, which were lower than the Hp phenotype reference ranges, which can be explained by depletion of circulating Hp stores. Myoglobinuria was most pronounced in players carrying a Hp 2-2 phenotype, which is associated with the lowest Hp reference range. Myoglobin clearance was inversely correlated with Hp 2-2 concentration. Correlation between myoglobinuria and biomarkers of muscle damage was weak. Neither age nor glomerular filtration rate were found to be confounders of myoglobinuria. When comparing myoglobinuria with training intensity, the number of sprints, average acceleration speed, and maximal speed were determining factors for predicting exercise-induced myoglobinuria. CONCLUSIONS: In athletes, plasma myoglobin binding capacity is depleted. Moderate myoglobinuria not only should be regarded as a muscle damage marker, but also should be interpreted as an indicator for Hp depletion. Apart from its significance as a biomarker for muscle damage and rhabdomyolysis, myoglobinuria in athletes should be a warning that the heme binding capacity of plasma Hp is depleted, indicating an exhausted defense against Fenton chemistry induced free radicals. Fenton chemistry is associated with free radical formation, which is to be avoided because of the causative relationship with inflammatory processes and tissue damage.

Carbamoylated Nail Proteins as Assessed by Near-Infrared Analysis are Associated with Load of Uremic Toxins and Mortality in Hemodialysis Patients.

Carbamoylation is an important risk factor for accelerated atherogenesis and mortality in patients undergoing hemodialysis (HD). We intended to explore whether carbamoylation as assessed by near-infrared (NIR) analysis of nail proteins is associated with (a) serum concentrations of representative uremic toxins and (b) mortality in HD patients. A total of 53 healthy volunteers and 84 consecutive HD patients were enrolled in this cross-sectional cohort study. Standard laboratory methods were used to measure routine parameters, whereas levels of uremic toxins were determined using reversed-phase high-performance liquid chromatography (RP-HPLC). Spectra of distal fingernail clippings were obtained using an Avantes NIR spectrometer and processed using chemometric data analysis. The second derivative of the peak intensity at 1494 nm attributed to N-H amide bands from NH2 of carbamoyl (-CONH2) groups was higher in HD patients than in control subjects (p < 0.0001). Peak intensity levels were associated with age and plasma levels of representative uremic toxins. Cox-regression analysis revealed a significant association with all-cause mortality, even after adjustment for age. In conclusion, our data revealed that carbamoylation as assessed by NIR analysis of nail proteins is associated with serum concentrations of uremic toxins and also with mortality in HD patients. Further research to explore whether it is a surrogate marker or a hard indicator of mortality risk is warranted.