Constantina Chrysochou

BACKGROUND AND OBJECTIVES: Higher phosphate is associated with mortality in dialysis patients but few prospective studies assess this in nondialysis patients managed in an outpatient nephrology clinic. This prospective longitudinal study examined whether phosphate level was associated with death in a referred population. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Patients (1203) of nondialysis chronic kidney disease (CKD) in the Chronic Renal Insufficiency Standards Implementation Study were assessed. Survival analyses were performed for quartiles of baseline phosphate relative to GFR, 12-month time-averaged phosphate, and baseline phosphate according to published phosphate targets. RESULTS: Mean (SD) eGFR was 32 (15) ml/min per 1.73 m(2), age 64 (14) years, and phosphate 1.2 (0.30) mmol/L. Cox multivariate adjusted regression in CKD stages 3 to 4 patients showed an increased risk of all-cause and cardiovascular mortality in the highest quartile compared with that in the lowest quartile of phosphate. No association was found in CKD stage 5 patients. Patients who had values above recommended targets for phosphate control had increased risk of all-cause and cardiovascular death compared with patients below target. The highest quartile compared with the lowest quartile of 12-month time-averaged phosphate was associated with an increased risk of mortality. CONCLUSIONS: In CKD stages 3 to 4 patients, higher phosphate was associated with a stepwise increase in mortality. As phosphate levels below published targets (as opposed to within them) are associated with better survival, guidelines for phosphate in nondialysis CKD patients should be re-examined. Intervention trials are required to determine whether lowering phosphate will improve survival.

BACKGROUND: Many physicians retain reservations regarding the routine prescription of renin-angiotensin blockade (RAB) in patients with atheromatous renovascular disease (ARVD). Conversely, these patients are in most need of the cardio- and renal protection offered by RAB. This reservation is mostly because of fear of precipitating acute renal deterioration. We aimed to study whether RAB can be used safely in ARVD patients and whether it altered their outcome. METHODS: Prospective observational study of all ARVD patients presenting to our tertiary referral centre from 1999-2009. Data capture included usage and tolerability of RAB, and correlation with endpoints of cardiovascular events, dialysis or death. RESULTS: Six hundred and twenty-one subjects were available for analysis. Mean age (SD) of the cohort was 71.3 (8.8) years, median (interquartile range) follow-up 3.1 (2.1, 4.8), range 0.2-10.61 years. Seventy-four patients had an intolerance to RAB at study entry. When utilized prospectively, RAB was tolerated in 357 of 378 patients (92%), and this was even seen in 54/69 (78.3%) patients with bilateral>60% renal artery stenosis (RAS) or occlusion. Patients (4/21) who were intolerant of RAB during follow-up (and 12 retrospectively intolerant), underwent renal revascularization which facilitated safe use of these medications post-procedure. On multivariate time-adjusted analysis, patients receiving RAB were significantly less likely to die (P=0.02). CONCLUSION: RAB is well tolerated even in patients with bilateral severe RAS and reduced mortality in a large group of ARVD patients. We recommend all ARVD patients be considered for RAB therapy unless an absolute contra-indication exists. Intolerance of these agents due to renal dysfunction should be considered an emerging indication for renal revascularization to facilitate their re-introduction.

BACKGROUND: Around 16% of all patients who present with atheromatous renovascular disease (ARVD) in the United States undergo revascularization. Historically, patients with advanced chronic kidney disease (CKD) have been considered least likely to show improvement in renal functional terms, or survival. We aimed to investigate whether differences in outcomes after revascularization compared to medical management might be observed in ARVD patients if stratified by their CKD classes. METHODS: Two prospective cohorts, a UK center with a traditionally conservative approach, and a German center who undertook a proactive revascularization approach, were compared. An improvement in renal function was defined as > 20% renal improvement at one year's follow-up. To improve validity and comparability, revascularized patients in the UK center were also used within analyses, RESULTS: 347 (UK conservative group), 89 (UK revascularized group), and 472 (German center) patients were included in the analysis. When subdivided by CKD stage, patient ages between the two centers were comparable. Improvements in renal function were observed in twice as many patients who underwent revascularization as compared to medical treatment, particularly in the latter CKD stages, 15.2 (German revascularization) vs. 0% in CKD 1-2, 12.2 (UK), and 32.8 (German) revascularization vs. 14.1% in CKD3, and 53.1 and 53.8 vs. 28.3 in patients with CKD 4-5. The improvements in eGFR were 10.2 (16) and 8.1 (12.5) ml/min/year in the German and UK revascularized groups, respectively, vs. -0.05 (6.8) ml/min/year in the medical cohort in CKD 4-5. Improvements in blood pressure control were noted at 1 year overall and within each CKD category. Multivariate analysis revealed that revascularization independently reduced the risk of death by 45% in all patients combined (RR 0.55, P = 0.013). CONCLUSIONS: Although this study has significant methodological limitations, it does shows that percutaneous renal revascularization can improve renal function in advanced CKD (stages 4-5), and that this can provide a survival advantage in prospective analysis.