Effects of Sevelamer Carbonate in Patients With CKD and Proteinuria: The ANSWER Randomized Trial
| Autor: | Donald E. Kohan, Veruska Lecchi, Sandro Mazzaferro, Antonio Bellasi, F. Mallamaci, D. Villa, G. Caridi, Davide Villa, Norberto Perico, Barbara Ruggiero, Olimpia Diadei, Matias Trillini, S. Peracchi, V. Lecchi, A. Cannata, Giuseppe Remuzzi, Carolina Aparicio, V. Fassino, Nadia Stucchi, Flavio Gaspari, Francesco Peraro, Antonio Cannata, Silvia Prandini, Francesca Mallamaci, G. Parlongo, Giulia Gherardi, Carmine Zoccali, S. Mazzaferro, B. Ruggiero, A. Celeste, Mario Cozzolino, Silvia Ferrari, Vincenzo Panuccio, Giovanni A. Giuliano, Lida Tartaglione, P. Ruggenenti, Elena Perticucci, G. Remuzzi, L. Tartaglione, Daniela Cugini, A. Perna, M. Trillini, F. Peraro, Annalisa Perna, Sergio Carminati, C. Aparicio, Piero Ruggenenti, Rocco Tripepi, Silverio Rotondi, S. Rotondi, Davide Martinetti, Fabiola Carrara, R. Tripepi, S. Ferrari, Paola Boccardo, Nadia Rubis |
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| Rok vydání: | 2018 |
| Předmět: |
Male
klotho 030232 urology & nephrology Angiotensin-Converting Enzyme Inhibitors Sevelamer sevelamer carbonate urologic and male genital diseases Renin-Angiotensin System Hyperphosphatemia chemistry.chemical_compound 0302 clinical medicine fgf-23 Ramipril chronic kidney disease (ckd) 030212 general & internal medicine Chelating Agents Proteinuria Cross-Over Studies clinical trial Middle Aged mineral metabolism Treatment Outcome Nephrology Drug Therapy Combination Female medicine.symptom Drug Monitoring ckd progression medicine.drug Glomerular Filtration Rate medicine.medical_specialty renin-angiotensin system (ras) medicine.drug_class Urology Renal function phosphate binder Phosphates 03 medical and health sciences Irbesartan medicine Humans Renal Insufficiency Chronic serum phosphate business.industry medicine.disease protein excretion Phosphate binder Fibroblast Growth Factor-23 chemistry inflammation proteinuria ras blockade Glycated hemoglobin business Kidney disease |
| Zdroj: | American journal of kidney diseases : the official journal of the National Kidney Foundation. 74(3) |
| ISSN: | 1523-6838 |
| Popis: | Rationale & Objective Hyperphosphatemia is associated with increased risk for chronic kidney disease (CKD) progression and reduced antiproteinuric effects of renin-angiotensin system (RAS) blockers. We investigated whether the phosphate binder sevelamer carbonate may enhance the antiproteinuric effect of RAS inhibitors in patients with CKD. Study Design Phase 2, randomized, controlled, open-label, crossover trial. Setting & Participants Between November 2013 and December 2014, we enrolled 53 patients with CKD with estimated glomerular filtration rates (eGFRs)>15mL/min/1.73m2 and residual proteinuria with protein excretion≥0.5g/24h despite maximal tolerated ramipril and/or irbesartan therapy from 2 nephrology units in Italy. Intervention After stratification by serum phosphate level, ≤4 or>4mg/dL, patients were randomly assigned to 3 months of sevelamer (1,600mg thrice daily) treatment followed by 3 months without sevelamer separated by a 1-month washout period or 3 months without sevelamer followed by 3 months with sevelamer, also separated by a 1-month washout period. Outcomes The primary outcome was 24-hour proteinuria (n=49patients). Secondary outcomes included measured GFR (using iohexol plasma clearance), office blood pressure (BP), serum lipid levels, levels of inflammation and bone metabolism biomarkers, urinary electrolyte levels, and arterial stiffness. Results Changes in proteinuria during the 3-month treatment with (from 1.36 [IQR, 0.77-2.51] to 1.36 [IQR, 0.77-2.60] g/24h) or without (from 1.36 [IQR, 0.99-2.38] to 1.48 [IQR, 0.81-2.77] g/24h) sevelamer were similar (P=0.1). Sevelamer reduced urinary phosphate excretion without affecting serum phosphate levels. Sevelamer reduced C-reactive protein (CRP), glycated hemoglobin, and total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels without affecting levels of office BP, measured GFR, fibroblast growth factor 23, klotho, intact parathyroid hormone, serum vitamin D, or other urinary electrolytes. Results were similar in the low- and high-phosphate groups. Sevelamer was well tolerated. Adverse events were comparable between treatment periods. One case of transient hypophosphatemia was observed during treatment with sevelamer. Limitations Short treatment duration, lower pretreatment proteinuria than expected. Conclusions 3-month sevelamer treatment did not reduce proteinuria in patients with CKD on maximal RAS blockade. Amelioration of inflammation and dyslipidemia with sevelamer treatment raises the possibility that it may confer benefit in patients with CKD beyond reduction of proteinuria. Funding Sanofi (Milan, Italy). Trial Registration Registered at ClinicalTrials.gov with study number NCT01968759. |
| Databáze: | OpenAIRE |
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