1. Phosphate may promote CKD progression and attenuate renoprotective effect of ACE inhibition
- Author
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Zoccali, Carmine, Ruggenenti, Piero, Perna, Annalisa, Leonardis, Daniela, Tripepi, Rocco, Tripepi, Giovanni, Mallamaci, Francesca, Remuzzi, Giuseppe, 'REIN Study Group' including Remuzzi, G, Tognoni, G, Ruggenenti, P, Bossini, N, Viola, Bf, Scolari, F, Maiorca, R, Cofano, F, Fellin, G, D'Amico, G, Dissegna, D, Brendolan, A, La Greca, G, Feriozzi, A, Ancarani, E, Gandini, E, D'Amato, I, Giangrande, A, Giannico, G, Vitale, O, Manno, C, Schena, Fp, Mazzi, A, Garini, G, Borghetti, A, Pisoni, R, Mosconi, L, Bertani, T, Scanferla, F, Bazzato, G, Oliva, E, Zoccali, C, Toti, G, Sisca, S, Maggiore, Q, Pignone, E, Boero, R, Piccoli, Giorgina Barbara, Piperno, R, Rosati, A, Salvadori, M, Ene Iordache, B, Remuzzi, A, Perna, A, Benini, R, Tammuzzo, L, Gaspari, F, Arnoldi, F, Ciocca, I, Signorini, O, Ferrari, S, Gritti, D, Roggeri, A, Del Priore, L, Cattaneo, D, Stucchi, N, Migone, L, Marubini, E, Del Favero, A, Ideo, G, Geraci, E, and Loi, U.
- Subjects
Ramipril ,Adult ,Male ,medicine.medical_specialty ,030232 urology & nephrology ,Urology ,Angiotensin-Converting Enzyme Inhibitors ,030204 cardiovascular system & hematology ,Aged ,Disease Progression ,Female ,Humans ,Middle Aged ,Phosphates ,Randomized Controlled Trials as Topic ,Renal Insufficiency, Chronic ,Renin-Angiotensin System ,Nephrology ,Nephropathy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Renin–angiotensin system ,medicine ,Renal Insufficiency ,Chronic ,Risk factor ,Ace inhibition ,Creatinine ,business.industry ,Confounding ,General Medicine ,Phosphate ,medicine.disease ,3. Good health ,Endocrinology ,chemistry ,business ,medicine.drug - Abstract
Phosphate may promote the onset and progression of chronic nephropathies. Here we evaluated the relationships between baseline serum phosphate levels, disease progression, and response to ACE inhibition in 331 patients with proteinuric nephropathies in the prospective Ramipril Efficacy In Nephropathy (REIN) trial. Independent of treatment, patients with phosphate levels in the highest two quartiles progressed significantly faster either to ESRD or to a composite endpoint of doubling of serum creatinine or ESRD compared with patients with phosphate levels below the median (P < 0.001). Results were similar when we analyzed phosphate as a continuous variable (P ≤ 0.004). The renoprotective effect of ramipril decreased as serum phosphate increased (P ≤ 0.008 for interaction); this modification of the treatment effect by phosphate persisted despite adjusting for potential confounders such as GFR and urinary protein. In summary, these data suggest that phosphate is an independent risk factor for progression of renal disease among patients with proteinuric CKD, and high levels of phosphate may even attenuate the renoprotective effect of ACE inhibitors. Future trials should test whether reducing serum phosphate improves renal outcomes and optimizes the renoprotective effect of ACE inhibition.
- Published
- 2011