doktorska disertacija
Nina Hojs (Avtor), Robert Ekart (Mentor), Robert Ekart (Član komisije za zagovor), Breda Pečovnik-Balon (Član komisije za zagovor), Ivan Krajnc (Član komisije za zagovor)

Povzetek

UVOD Kronična ledvična bolezen (KLB) predstavlja svetovni zdravstveni problem zaradi naraščajoče incidence, prevalence, slabih izidov zdravljenja in visokih stroškov zdravljenja. Proteinurija in albuminurija sta pokazatelja napredovanja ledvične bolezni, tveganja za nastanek končne ledvične odpovedi, srčno-žilne obolevnosti in umrljivosti. Zato je zdravljenje proteinurije in albuminurije eden od ciljev obravnave bolnikov s KLB. V zadnjem času so v ospredju raziskave o vlogi analogov vitamina D, še posebej parikalcitola, pri zmanjšanju proteinurije in albuminurije. Namen naše raziskave je bil ugotoviti vpliv zdravljenja s parikalcitolom pri nedializnih bolnikih s KLB in mineralno-kostno boleznijo na ledvične in srčno-žilne dejavnike tveganja. BOLNIKI IN METODE V raziskavo smo vključili 45 nedializnih bolnikov s KLB (31 moških in 14 žensk), povprečne starosti 61,98±11,87 let (razpon 31–84 let), vsi so bili belci. Vse bolnike smo ob prvem obisku v ambulanti klinično pregledali, opravili smo laboratorijske preiskave krvi in urina ter merjenje krvnega tlaka (ambulantna meritev in 24-urni krvni tlak). Na podlagi uveljavljenih smernic za zdravljenje mineralno-kostne bolezni v sklopu KLB (Kidney Disease Improving Global Outcome (KDIGO) 2009) smo bolnikom, ki so imeli proteinurijo in intaktni parathormon ≥ 65 pg/ml, ob prvem obisku uvedli parikalcitol (1 μg/dan). Bolnike smo nato spremljali na 3 mesece. Parikalcitol so jemali celokupno 6 mesecev, po njegovi ukinitvi smo jih spremljali še 6 mesecev. REZULTATI Terapija s parikalcitolom je statistično značilno znižala albumin/kreatinin v urinu, 24-urno albuminurijo in 24-urno proteinurijo, 6 mesecev po ukinitvi terapije sta albumin/kreatinin v urinu in 24-urna albuminurija statistično značilno porastla, 24-urna proteinurija pa se ni statistično značilno spremenila. Med terapijo s parikalcitolom sta serumski kreatinin in cistatin C statistično značilno porastla, ocenjena hitrost glomerulne filtracije po Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) kreatininski formuli in enostavni cistatinski formuli je upadla. Serumski kreatinin je 6 mesecev po zaključeni terapiji s parikalcitolom neznačilno upadel, ocenjena hitrost glomerulne filtracije, izračunane na osnovi CKD-EPI kreatininske formule, pa je statistično značilno porastla. Šest mesecev po zaključeni terapiji s parikalcitolom sta serumski cistatin C in na osnovi njega izračunana ocenjena hitrost glomerulne filtracije ostala približno enaka. Ob terapiji s parikalcitolom, niti po njegovi ukinitvi, se vsi parametri 24-urnega krvnega tlaka, vnetni pokazatelji, urat, troponin I (TnI) in možganski natriuretični peptid (NT-proBNP) niso statistično značilno spremenili. Ob terapiji s parikalcitolom se je statistično značilno znižal holesterol v lipoproteinu majhne gostote (LDL holesterol). Šest mesecev po ukinitvi parikalcitola ni prišlo do statistično značilnih sprememb holesterola. Apolipoprotein A1, B, lipoprotein(a), rastni faktor fibroblastov-23 (FGF-23) in homocistein smo spremljali le ob vključitvi v raziskavo in 12 mesecev zatem. Apolipoprotein A1 je v opazovanem obdobju statistično značilno upadel, FGF-23 je statistično značilno porastel, drugi parametri se niso statistično značilno spremenili. ZAKLJUČEK Z našo raziskavo smo dokazali, da 6-mesečno zdravljenje s parikalcitolom (1 µg/dan) pri nedializnih bolnikih s KLB in mineralno-kostno boleznijo zmanjša proteinurijo in albuminurijo, zniža LDL holesterol in ne vpliva na 24-urni krvni tlak, vnetne pokazatelje, urat, TnI, NT-proBNP. Ledvična funkcija se je, kljub zmanjšanju proteinurije in albuminurije, v času zdravljenja poslabšala. Šest mesecev po zaključeni terapiji s parikalcitolom je albuminurija porastla, medtem ko se proteinurija ni spremenila. Ledvična funkcija je glede na serumski cistatin C ostala enaka, glede na serumski kreatinin pa se je izboljšala. Parametri dislipidemije, 24-urni krvni tlak, vnetni pokazatelji, urat, TnI in NT-proBNP se niso spremenili.

Ključne besede

24-urni krvni tlak;albuminurija;kronična ledvična bolezen;parikalcitol;proteinurija;serumski cistatin C;srčno-žilne bolezni;Bolezni izločal;Disertacije;Kronična ledvična odpoved;Komplikacije;Zdravljenje;

Podatki

Jezik: Slovenski jezik
Leto izida:
Tipologija: 2.08 - Doktorska disertacija
Organizacija: UM - Univerza v Mariboru
Založnik: N. Hojs]
UDK: 616.61-008.6:577.161.2:612.392.015.6+615.35(043.3)
COBISS: 512499512 Povezava se bo odprla v novem oknu
Št. ogledov: 1853
Št. prenosov: 208
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Sekundarni jezik: Angleški jezik
Sekundarni naslov: The effect of paricalcitol on proteinuria in non-dialysis chronic kidney disease patients
Sekundarni povzetek: INTRODUCTION Chronic kidney disease (CKD) is a worldwide health problem because of growing incidence, prevalence, poor treatment outcomes and high costs of treatment. Proteinuria and albuminuria are important signs of CKD progression, risk of chronic kidney failure, cardiovascular disease and death. Therefore treatment of proteinuria and albuminuria is one of the goals in managing CKD patients. Latest studies explore the role of vitamin D analogues, especially paricalcitol, in the treatment of proteinuria and albuminuria. The aim of our study was to explore the effect of paricalcitol treatment in non-dialysis CKD patients with mineral and bone disorder on renal and cardiovascular risk factors. PATIENTS AND METHODS Forty-five non-dialysis CKD patients (31 men, 14 women), aged 61.98±11.87 years (range 31-84 years), all of white race, were included in our study. At the beginning of our study all patients were clinically examined, laboratory tests were taken and blood pressure was measured (single measurement and 24-hour ambulatory blood pressure measurement). Based on guidelines for the treatment of mineral and bone disorder in CKD (Kidney Disease Improving Global Outcome (KDIGO) 2009) patients with proteinuria and intact parathormone ≥ 65 pg/ml received paricalcitol (1 µg/day). Patients were then followed every 3 months. They received paricalcitol for 6 months, after paricalcitol withdrawal we followed them for 6 more months. RESULTS Paricalcitol treatment significantly reduced urinary albumin/creatinine ratio, 24-hour albuminuria and 24-hour proteinuria. Six months after drug withdrawal urinary albumin/creatinine ratio and 24-hour albuminuria increased significantly, 24-hour proteinuria did not change significantly. Serum creatinine and cystatin C significantly increased during treatment, estimated glomerular filtration rate (eGFR) based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine formula and simple cystatin C formula decreased. After drug withdrawal serum creatinine did not change significantly, eGFR based on CKD-EPI creatinine formula significantly increased. After drug withdrawal serum cystatine C and eGFR based on simple cystatine C formula did not change significantly. Treatment and paricalcitol withdrawal did not affect 24-hour ambulatory blood pressure, inflammation, urate, troponin I (TnI), brain natriuretic peptide (NT-proBNP). Low-density lipoprotein cholesterol (LDL cholesterol) significantly decreased during paricalcitol treatment. Six months after paricalcitol withdrawal it did not change significantly. We observed apolipoprotein A1, B, lipoprotein(a), fibroblast growth factor-23 (FGF-23) and homocystein at the beginning and end of our study. Apolipoprotien A1 significantly decreased during this time, FGF-23 significantly increased, other parameters did not change significantly. CONCLUSION Six-month paricalcitol treatment (1 µg/day) in non-dialysis CKD patients with bone and mineral disorder significantly reduces proteinuria, albuminuria, LDL cholesterol, while it does not affect 24-hour ambulatory blood pressure, inflammation, urate, TnI, NT-proBNP. Kidney function decreased despite the reduction in proteinuria and albuminuria. Six months after paricalcitol withdrawal albuminuria increased significantly, while proteinuria did not change significantly. According to serum cystatine C kidney function remained stable, while it improved according to serum creatinine. Withdrawal of paricalcitol did not affect 24-hour ambulatory blood pressure, inflammation, urate, TnI and NT-proBNP.
Sekundarne ključne besede: ambulatory blood pressure monitoring;albuminuria;cardiovascular disease;chronic kidney disease;paricalcitol;proteinuria;serum cystatin C;
URN: URN:SI:UM:
Vrsta dela (COBISS): Doktorska disertacija
Strani: 112 str.
ID: 8752613