Učinkovitost in varnost parikalcitola za zmanjšanje proteinurije pri bolnikih s presajeno ledvico: randomizirana, dvojno-slepa, s placebom kontrolirana raziskava

Oblak, Manca (author), Arnol, Miha (mentor)

Uvod. Bolniki s presajeno ledvico, pri katerih je prisotna bolezenska proteinurija imajo večje tveganje za napredovanje kronične ledvične bolezni (KLB) presadka, odpoved presajene ledvice ter zvečano tveganje za srčno-žilne dogodke. V naši raziskavi smo proučevali vpliv aktivatorja receptorja za vitamin D, parikalcitola, pri bolnikih s presajeno ledvico in proteinurijo kljub optimalnem enotirnem zdravljenju z zaviralci renin-angiotenzin-aldosteron sistema (RAAS). Preiskovanci in metode. V randomizirano, s placebom kontrolirano, dvojno slepo raziskavo smo vključili bolnike s presajeno ledvico, pri katerih je bilo razmerje med beljakovinami in kreatininom v seču (UPCR) &#8805;20 mg/mmol kljub optimalnem enotirnem zdravljenju z zaviralci RAAS. Bolniki so bili naključno randomizirani v skupino, ki je jemala parikalcitol 2 µg dnevno ali placebo. Primarni cilj raziskave je bil odstotek spremembe geometrične sredine UPCR, glavni sekundarni cilji pa odstotek spremembe geometrične sredine razmerja med albuminom in kreatininom v seču (UACR) in 24-urne proteinurije od izhodiščne do zadnje meritve v času zdravljenja. Primerjave vseh ciljev raziskave so temeljile na analizi z-namenom-zdravljenja (angl. intention-to-treat). Raziskava je registrirana v podatkovni bazi kliničnih raziskav ClinicalTrials.gov, številka NCT01436747. Rezultati. Leta 2012 je imelo 190 od 572 bolnikov s presajeno ledvico (33%) UPCR &#8805;20 mg/mmoL. Randomizirali smo 168 bolnikov, parikalcitol je jemalo 83, placebo 85 bolnikov. Vsi bolniki so vzeli vsaj en odmerek zdravila, tako da smo pridobili meritve UPCR ob izhodišču in najmanj eno meritev v fazi zdravljenja. Sprememba UPCR je bila v skupini, ki je jemala parikalcitol -38 % (74 do 46 mg/mmoL; 95 % interval zaupanja [IZ]) -45 % do -31 %), v skupini, ki je jemala placebo 21 % (55 do 63 mg/mmoL; 95 % IZ 9 % do 36 %) (P <0,001). Sprememba UACR in izločanja beljakovin v 24-urnem seču je bila v skupini, ki je jemala parikalcitol -47 % (95 % IZ -54 % do -38 %) in -35 % (95 % IZ -42 % do -28 %), v skupini, ki je jemala placebo pa 11% (95% IZ -5% do 29%) in 19% (95% IZ 8% do 30%). Incidenca blage hiperkalciemije je bila večja v skupini, ki je jemala parikalcitol in je po zmanjšanju odmerka zdravila izzvenela. Zaključek. Pri bolnikih s presajeno ledvico dodatek parikalcitola 2 µg dnevno zmanjša rezidualno proteinurijo, zato bi ga lahko uporabljali za zmanjšanje tveganja odpovedi delovanja presajene ledvice.

• Language: Slovenian
• Keywords: presaditev ledvice, parikalcitol, proteinurija, albuminurija, biološki pokazatelji
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2018
• PID: 20.500.12556/RUL-104964
• COBISS.SI-ID: 297138944
• Publication date in RUL: 19.10.2018

Secondary language

• Language: English
• Title: Efficacy and safety of paricalcitol for reduction of proteinuria in kidney transplant recipients: randomised, double-blind, placebo-controlled trial

Abstract

Introduction. Kidney transplant recipients with proteinuria have an increased risk of graft failure. We studied the effects of the vitamin D receptor activator paricalcitol in kidney transplant recipients with residual proteinuria after optimization of the renin-angiotensin-aldosteron system (RAAS) blockade. Patients and Methods. In this single-centre, placebo-controlled, double-blind trial, we enrolled kidney transplant recipients with urinary protein-to-creatinine ratio (UPCR) &#8805;20 mg/mmol despite optimization of the RAAS blockade during the run-in-phase. Patients were randomly assigned to receive 24 weeks’ treatment with 2 µg/day paricalcitol or placebo. Primary endpoint was the percent change in geometric mean UPCR, and secondary endpoints included the percent change in geometric mean urinary albumin-to-creatinine ratio (UACR) and 24-hour proteinuria from baseline to last measurement during treatment. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01436747. Results. In 2012, 190 of 572 prevalent kidney transplant recipients (33%) had UPCR &#8805;20 mg/mmol. Of the 168 patients who undergo randomization, 83 were allocated to paricalcitol, and 85 to placebo; all patients received at least one dose of study drug and had UPCR data at baseline and at least one time-point during treatment. Change in UPCR was -38% (from 74 to 46 mg/mmol; 95% CI -45% to -31%) in the paricalcitol group and 21% (from 55 to 63 mg/mmol; 95% CI 9% to 36%) in the placebo group (P<0.001). Change in UACR and 24-hour proteinuria was -47% (95% CI -54% to -38%) and -35% (95% CI -42% to -28%) in the paricalcitol group, and 11% (95% CI -5% to 29%) and 19% (95% CI 8% to 30%) in the placebo group, respectively. Incidence of mild hypercalcemia was higher in the paricalcitol group. A reduction of the study drug dose lead to normal serum calcium levels in all patients. Conclusion. In kidney transplant recipients, addition of 2 µg/day paricalcitol lowers residual proteinuria, and could be used as an effective approach to lower graft failure risk.

• Keywords: kidney transplantation, paricalcitol, proteinuria, albuminuria, biomarkers