Značaj određivanja biomarkera resorpcije i stvaranja kostiju kod pacijenata sa krajnjim stadijumom bolesti bubrega

Abstract

Vodiči za poboljšanje kvaliteta života i edukaciju pacijenata sa krajnjim stadijumom bolesti bubrega (Kidney Disease Outcomes Quality Initiatives, KDOQI), objavljeni od strane američke Nacionalne Fondacije za bubreg (NKF) ukazuju na značaj biomarkera metabolizma kostiju koje bi trebalo određivati kod pacijenata sa krajnjim stadijumom bolesti bubrega (KSBB). Prema NKF pacijenti sa KSBB (stadijum 5) su oni čija je GFR ispod 15 mL/min/1,73 m2. To su predijalizni pacijenti, pacijenti koji su na terapiji hemodijalizom (HD) ili kontinuiranom ambulatornom peritonealnom dijalizom (CAPD). Osnovni serumski biomarkeri koje bi trebalo određivati kod svih pacijenata sa petim stadijumom bolesti bubrega su joni kalcijuma (Ca), joni neorganskog fosfata (P), joni magnezijuma (Mg), ukupna alkalna fosfataza (ALP), intaktni paratiroidni hormon (iPTH) i 25-hidroksi vitamin D (25D). Međutim, metabolizam kostiju najpouzdanije mogu da prikažu jedino biomarkeri koje stvaraju ćelije kostiju, osteoblasti i osteoklasti. Aktivnost osteoblasta, ćelija koje su odgovorne za stvaranje kostiju, najbolje odražavaju nivoi koštanog izoenzima alkalne fosfataze (BALP), koji je visoko specifičan za koštano tkivo. Aktivnost osteoklasta, ćelija koje su odgovorne za resorpciju kostiju, specifično odražavaju nivoi tartarat rezistentne kisele fosfataze (TRAP). Dobar marker resorpcije kostiju jeste i beta-karboksi terminalni deo ukrštenih veza kolagena I, beta-CrossLaps (beta-CTx). Specifični serumski biomarkeri kostiju predstavljaju "biohemijsku biopsiju" značajnu za lakšu procenu i praćenje metabolizma kostiju. Cilj ovog rada bio je da se utvrdi značaj određivanja biomarkera resorpcije i stvaranja kostiju kod KSBB pacijenata. Ispitivanjem je obuhvaćeno 40 predijaliznih pacijenata (18 žena i 22 muškarca) starosne dobi 25−79, 114 pacijenata na CAPD (49 žena i 65 muškaraca) starosne dobi 30−84 i 112 pacijenata na HD (53 žene i 59 muškaraca) starosne dobi 25−79. Prosek trajanja lečenja hemodijalizom bio je 76 meseci, dok su pacijenti na CAPD bili 35 meseci. Planirani biomarkeri formiranja i resorpcije kostiju su se određivali u serumu ispitivanih pacijenata na dan uzorkovanja i to kod predijaliznih i CAPD pacijenata kada su dolazili na rutinske kontrolne preglede, a kod pacijenata na HD neposredno pre terapije dijalizom. Radi određivanja referentnih intervala u serumu, analizirani biomarkeri su određivani i u grupi od 50 zdravih dobrovoljaca (25 žena i 25 muškaraca) starosne dobi od 20−70 godina. ALP, TRAP, Ca, P i Mg su određeni fotometrijski (Olympus AU2700 ISE). BALP je određen zonskom elektroforezom (Sebia Hydrasis), beta-CTx i iPTH su određeni ECLIA metodom (Rosche Elecsys), a 25D HPLC-om reverznih faza (ChromLineR Clinical HPLC software Version 4.20). Određivanje analiziranih biomarkera u serumu se smatralo pouzdanim na osnovu koeficijenata varijacije dobijenih testiranjem preciznosti u seriji (Kv: 0,6%−3,3%) i iz dana u dan (Kv: 1,0%−3,6%). Ustanovljena je normalna raspodela vrednosti za svaki od analiziranih biomarkera kod predijaliznih, HD i CAPD pacijenata. Kod sve tri ispitivane grupe pacijenata uočen je uticaj pola na vrednosti iPTH, kao i na vrednosti neorganskog fosfata kod HD pacijenata i na vrednosti CaxP kod CAPD pacijenata. Međutim, uticaj starosti je kod sve tri grupe pacijenata uočen jedino na vrednosti BALP. Takođe, dužina trajanja HD imala je uticaj na vrednosti ALP BALP, a CAPD samo na vrednosti jona magnezijuma...

Guidelines for improving the quality of life and education of patients with end-stage renal disease (Kidney Disease Outcomes Quality Initiatives, KDOQI), published by the U.S. National Kidney Foundation (NKF), indicate the importance of biomarkers of bone metabolism that should be determined in patients with end-stage renal disease (ESRD). According to the NKF, ESRD patients (stage 5) are those with a GFR below 15 ml/min/1.73 m2. These are predialysis patients, patients who are treated with hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). The basic serum biomarkers that could be determined in all patients with the fifth stage renal disease are: calcium ions (Ca), inorganic phosphate ions (P), magnesium ions (Mg), the total alkaline phosphatase (ALP), an intact parathyroid hormone (iPTH) and 25-hydroxy vitamin D (25D). However, the most reliable bone metabolism can be represented only by biomarker created by bone cells, osteoblasts and osteoclasts. The activity of osteoblasts, the cells responsible for bone formation, is well expressed by the levels of bone alkaline phosphatase isoenzymes (BALP), which is highly specific for bone tissue. The activity of osteoclasts, the cells responsible for bone resorption, specifically reflect levels of tartrate resistant acid phosphatase (TRAP). A good marker of bone resorption is the beta-carboxy terminal telopeptide of collagen type I, beta-CrossLaps (beta-CTx). Specific serum biomarkers of bone are "biochemical biopsy" important to facilitate the assessment and monitoring of bone metabolism. The aim of this study was to assess the usefulness of biomarkers of bone resorption and bone formation in ESRD patients. The study included 40 predialysis patients (18 women and 22 men) aged 25−79, 114 patients on CAPD (49 women and 65 men) aged 30−84 and 112 patients on HD (53 women and 59 men) aged 25−79. Average duration of the hemodialysis treatment was 76 months, while patients on CAPD treated 35 months. The analysed biomarkers of bone formation and resorption were determined in the serum of patients on the day of sampling and in predialysis patients and in patients on CAPD when they came to the routine check-ups, and in patients on HD immediately before dialysis therapy. To determine the reference intervals, analyzed biomarkers were measured in a group of 50 healthy volunteers (25 women and 25 men) aged 20−70 years. ALP, TRAP, Ca, P and Mg were determined photometrically (Olympus AU2700 ISE). BALP values were determined with zone electrophoresis (SEBIA Hydrasis), beta-CTx and iPTH values were determined with ECLIA (Elecsys Rosche) and 25D values were detrmined by HPLC with reversed phase detection (HPLC ChromLineR Clinical software Version 4:20). Determination of the analysed biomarkers is considered reliable based on the coefficients of variation obtained by precision testing in the series (Cv: 0.6%−3.3%) and from day to day (Cv: 1.0%−3.6%). We established the normal distribution of the values for each of the analysed biomarkers in predialysis and dialysed patients. There were different values of iPTH, P and CaxP levels in the all analysed groups according to gender. However, the effect of age was observed only on the values of BALP. Duration of the dialysis had impact only on the values of ALP and BALP in HD patients and on Mg levels in CAPD patients...