Gastrointestinal-specific patient-reported outcome instruments differentiate between renal transplant patients with or without GI complications.

BACKGROUND: Gastrointestinal (GI) complications are frequently reported postrenal transplant and are often associated with immunosuppressant regimens including mycophenolate mofetil (MMF). This study evaluated the ability of two GI-specific patient-reported outcome (PRO) instruments to differentiate between patients with and without GI complaints. METHODS: Discriminant validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI), as well as two generic instruments (Psychological General Well-Being Index (PGWB) and EQ-5D, was assessed in a multinational study of renal transplant recipients. Patients received therapy that included a calcineurin inhibitor and MMF. Both t-tests and ANOVAs were used to examine differences between patients with and without GI complaints, among levels of severity, and between patients reporting presence/absence of specific GI side effects. RESULTS: Of 96 patients recruited (56% male), 43% had none, 39% mild, 13% moderate, and 6% severe GI symptoms. All GSRS subscales and the GIQLI total and four of the five subscale scores significantly differentiated between patients with/without GI complications (P < .05). The PGWB total score and three subscales, the EQ-5D significantly differentiated between the two groups (P < .05). Only GI-specific instruments discriminated between some severity levels; for example, the GSRS abdominal pain subscale discriminated between patients at all levels of severity (P < .05). The GIQLI total score and symptoms subscale differentiated between patients with no symptoms and those with mild or moderate or severe symptoms (P < .05). CONCLUSIONS: The GSRS and GIQLI differentiated between patients with/without GI side effects and by symptom severity better than did generic instruments, demonstrating excellent discriminant ability in this population.

Increase in angiotensin II type 1 receptor expression immediately after ischemia-reperfusion in isolated rat hearts.

BACKGROUND: Myocardial ischemia is known to upregulate the systemic renin-angiotensin system, which influences myocardial ischemic events by affecting hemodynamics and hemostatic activity. This study was designed to examine whether angiotensin II (Ang II) receptor expression in the myocardium is altered immediately after ischemia-reperfusion. METHODS AND RESULTS: Isolated buffer-perfused Sprague-Dawley rat hearts were subjected to continuous perfusion (control, n=5) or to 25 minutes of global ischemia followed by 30 minutes of reperfusion (n=10). Autoradiographic analysis for Ang II receptors of multiple myocardial sections was performed. Whereas continuous perfusion of hearts resulted in minor changes in coronary perfusion pressure (CPP), left ventricular end-diastolic pressure (LVEDP), and developed left ventricular pressure (dLVP=LVSP-LVEDP), ischemia-reperfusion caused a marked increase in CPP and LVEDP and a decrease in dLVP, indicating severe cardiac dysfunction. Concurrently, total myocardial Ang II receptor expression was greater (P<.05) in hearts subjected to ischemia-reperfusion than in the continuously perfused control hearts. Most of the increase in Ang II receptor expression was due to an increase in type 1 receptor (AT1) expression (34.6+/-6.5 versus 18.2+/-4.4 fmol/g, P<.05), because Ang II type 2 receptor expression was unaffected. To examine the importance of AT1 receptor expression, another group of isolated rat hearts (n=5) was perfused with buffer containing losartan (10(-5) mol/L) and subjected to ischemia followed by reperfusion. Perfusion of hearts with losartan attenuated the ischemia-reperfusion-induced cardiac dysfunction. Perfusion of hearts with losartan also blocked the ischemia-reperfusion-induced increase in myocardial AT1 binding. CONCLUSIONS: These observations indicate that myocardial AT1 expression increases immediately after ischemia-reperfusion and contributes to cardiac dysfunction.