Abstract
Background and Aims
Patients with Fabry disease frequently develop progressive Fabry nephropathy, hypertrophic cardiomyopathy with arrhythmias and subsequent death, transient ischemic attacks and early cerebral stroke. Homoarginine is an amino acid derivative, mainly produced in the kidney from its precursor lysine. Homoarginine may increase nitric oxide availability, decrease the release of cytokines, modulate the renin-angiotensin-aldosterone system and improve cardiac contractility. We hypothesize that high homoarginine levels associate with less clinical symptoms and better renal function in patients with Fabry disease.
Method
This study investigated the homoarginin status and its association with renal function, left ventricular (LV) mass and adverse clinical symptoms in patients with Fabry disease. Homoarginine was measured by high-performance liquid chromatography in 162 patients who were genetically proven to have Fabry disease. GFR was determined by DTPA clearance. LV mass and cardiomyopathy were assessed by magnetic resonance imaging and echocardiography. In cross-sectional analyses, associations with adverse clinical outcomes were determined by linear and binary logistic regression analyses, respectively, and were adjusted for age, sex, and BMI.
Results
Patients had a mean age of 39±14 years and 41% were male. The mean homoarginine concentration was 2.0±1.0 µmol/l. Patients had a mean BMI of 23.7±4.5 kg/m2 and a mean GFR of 93±37 ml/min. Homoarginine was significantly correlated with GFR and proteinuria. The better the homoarginine status of the patients, the higher was their GFR (r=0.20, p=0.04) and the lower proteinuria (r=-0.21, p=0.03). Furthermore, LV mass was significantly higher with lower homoarginine levels (r=-0.30, p<0.01). Patients of the lowest homoarginine tertile had a 4-fold higher risk of myocardial hypertrophy (OR 4.17, 95% CI 1.44-12.02), especially with septal and posterior hypertrophy, compared to those of the upper tertiles. Similarly, patients of the lowest homoarginine tertile had a higher rate of angina pectoris (OR 4.2, 95% CI 1.3-13.3) and chronic pain (OR 4.1, 95% CI 1.7-10.1), compared to patients of the upper tertiles. At lower homoarginine status, the median levels of proteinuria increased, as well as the prevalence rates of heart failure and the need for analgesic therapy.
Conclusion
In conclusion, low homoarginine status was strongly associated with cardiomyopathy, renal function and adverse clinical symptoms in patients with Fabry disease. Whether homoarginine supplementation improves complications of Fabry disease, requires a randomized controlled trial.
SP178PODOCYTURIA IN FABRY DISEASE IS ELEVATED IN UNTREATED VS TREATED ADULT PATIENTS AND DOES NOT CORRELATE WITH PROTEINURIA OR RENAL FUNCTION