Early detection of renal damage caused by fumaric acid ester therapy by determination of urinary ß2-microglobulin.

BACKGROUND: Fumaric acid esters are considered efficacious and safe drugs for the treatment of psoriasis. Renal damage, caused either by acute renal injury or Fanconi syndrome, is a recognized side-effect of this therapy. OBJECTIVES: To investigate whether the measurement of urinary excretion of ß2-microglobulin, a marker of renal proximal tubular dysfunction, allows early detection of kidney damage before an increase in serum creatinine or significant proteinuria occurs. METHODS: Urinary ß2-microglobulin excretion was measured regularly in 23 patients undergoing fumaric acid ester therapy. RESULTS: Urinary ß2-microglobulin remained normal in all 10 male patients. Three (23%) out of 13 female patients experienced an increase in urinary ß2-microglobulin excretion. In two of these patients a sharp increase was observed in association with high doses. One further patient had moderately elevated levels on rather low doses of fumaric acid esters. After discontinuing treatment, urinary ß2-microglobulin levels returned to normal within a few weeks. CONCLUSION: Determination of urinary ß2-microglobulin possibly allows early detection of renal damage by fumaric acid esters. Female patients seem to be prone to this side-effect, especially when taking high doses.

A simple score predicts future cardiovascular events in an inception cohort of dialysis patients.

Vascular calcifications are very common in dialysis patients and have been shown to be associated independently with outcome. However, all of these studies used prevalent patients on dialysis since many years. We investigated vascular calcifications in an inception cohort of dialysis patients and followed them for cardiovascular disease outcomes during an average observation period of 66 months. One hundred and fifty-four Caucasian dialysis patients were enrolled in one Austrian dialysis center. Standardized plain radiographs from the pelvis and calves were carried out in all patients at the start of dialysis therapy. Vascular calcifications were assessed by a single radiologist. At the start of renal replacement therapy, 67.5% of the patients showed vascular calcifications. During follow-up, 29.9% of patients suffered a cardiovascular event. An additive 'vascular risk score', constructed from the presence of vascular calcifications and/or previous cardiovascular events before the start of dialysis treatment, showed the strongest independent association with cardiovascular events in the Cox regression model adjusted for various risk factors. The presence of each of these two conditions was associated with a hazard ratio of 2.03 (95% confidence interval 1.19-3.46) and a hazard ratio twice as high if both conditions were present. In summary, vascular calcifications on plain X-rays of pelvis and calves are largely present in incident dialysis patients. A history of a cardiovascular event in the predialysis period together with vascular calcifications at the beginning of dialysis therapy is a more powerful predictor of a cardiovascular event than age, smoking, diabetes, or other traditional risk factors.

A method for measuring picosecond phenomena in photolabile species: the emission lifetime of bacteriorhodopsin.

We have measured the emission lifetime of bacteriorhodopsin at physiological temperatures to be 15 +/- 3 ps using a technique which employs a mode-locked dye laser, a sum frequency light gate, and a continuous flow system. We observe no concentration dependence of the lifetime over the range of 1.1 X 10(-4) M to 1.0 X 10(-5) M. We conclude that the emission which we observe comes from bacteriorhodopsin and not one of its photochemically produced intermediates, and that the emission cannot originate from the state into which light is absorbed.