title: Phosphate may promote CKD progression and attenuate renoprotective effect of ACE inhibition.
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.
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy. carmine.zoccali@tin.it
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.forename: Annalisa
authors.initials: A
authors.lastname: Perna
authors.forename: Daniela
authors.initials: D
authors.lastname: Leonardis
authors.forename: Rocco
authors.initials: R
authors.lastname: Tripepi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood*; D017257:Ramipril / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010710:Phosphates; D017257:Ramipril