title: Measuring and estimating GFR and treatment effect in ADPKD patients: results and implications of a longitudinal cohort study.
abstract: Trials failed to demonstrate protective effects of investigational treatments on glomerular filtration rate (GFR) reduction in Autosomal Dominant Polycystic Kidney Disease (ADPKD). To assess whether above findings were explained by unreliable GFR estimates, in this academic study we compared GFR values centrally measured by iohexol plasma clearance with corresponding values estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) and abbreviated Modification of Diet in Renal Disease (aMDRD) formulas in ADPKD patients retrieved from four clinical trials run by a Clinical Research Center and five Nephrology Units in Italy. Measured baseline GFRs and one-year GFR changes averaged 78.6±26.7 and 8.4±10.3 mL/min/1.73 m(2) in 111 and 71 ADPKD patients, respectively. CKD-Epi significantly overestimated and aMDRD underestimated baseline GFRs. Less than half estimates deviated by <10% from measured values. One-year estimated GFR changes did not detect measured changes. Both formulas underestimated GFR changes by 50%. Less than 9% of estimates deviated <10% from measured changes. Extent of deviations even exceeded that of measured one-year GFR changes. In ADPKD, prediction formulas unreliably estimate actual GFR values and fail to detect their changes over time. Direct kidney function measurements by appropriate techniques are needed to adequately evaluate treatment effects in clinics and research.
authors.affiliation: Clinical Research Center for Rare Diseases Aldo & Cele Daccò, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.forename: Flavio
authors.initials: F
authors.lastname: Gaspari
authors.forename: Antonio
authors.initials: A
authors.lastname: Cannata
authors.forename: Fabiola
authors.initials: F
authors.lastname: Carrara
authors.forename: Claudia
authors.initials: C
authors.lastname: Cella
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferrari
authors.forename: Nadia
authors.initials: N
authors.lastname: Stucchi
authors.forename: Silvia
authors.initials: S
authors.lastname: Prandini
authors.forename: Bogdan
authors.initials: B
authors.lastname: Ene-Iordache
authors.forename: Olimpia
authors.initials: O
authors.lastname: Diadei
authors.forename: Norberto
authors.initials: N
authors.lastname: Perico
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ondei
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
authors.forename: Erasmo
authors.initials: E
authors.lastname: Buongiorno
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Messa
authors.forename: Mauro
authors.initials: M
authors.lastname: Dugo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007472:Iohexol / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009398:Nephrology / Q000379:methods; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D015203:Reproducibility of Results; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D007472:Iohexol