Odnos koncentracija citokina i biokemijskih pokazatelja koštane pregradnje u serumu bolesnika s presađenim bubregom [ Relationship of cytokine concentrations and biochemical bone turnover markers in kidney transplant recipients serum ]

Šmalcelj, Ružica (2004) Odnos koncentracija citokina i biokemijskih pokazatelja koštane pregradnje u serumu bolesnika s presađenim bubregom [ Relationship of cytokine concentrations and biochemical bone turnover markers in kidney transplant recipients serum ]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Bone metabolism disorders are present in kidney transplant recipients even after a satisfactory graft function has been attained. Very probably, these disorders are a consequence of earlier, pretransplant disorders that persist after the transplant. After the transplant, however, new factors with a negative impact on bone metabolism develop (immunosuppressant drugs). In patients with a good and stable kidney function, the degree of bone turnover is estimated by non-invasive bone turnover markers. The following serum/urine parameters have been established for the estimate of the degree of bone turnover: calcium, inorganic phosphates, iPTH, osteocalcin, procollagen I, bone alkaline phosphatase, deoxypyridinoline cross links. Assessed are serum concentrations of IL-6, soluble IL-6 receptor, TGFβ1, TNFα – cytokines/receptor known to have a role in the process of bone turnover. Sixty-four patients were included in the study, 18 of them being in their first posttransplant year. In the remaining 46, the posttransplant period was longer than 12 months. In 16 patients of the 18 in whom the investigation was done during the first posttransplant year, a minimum of 2 months elapsed between the transplant and the measurements. According to its markers, bone turnover was accelerated in the majority of patients. Deoxypyridinoline cross-link concentration was higher in women than in men. The duration of dialysis treatment is a risk factor for a more rapid bone turnover after kidney transplantation. It was noted that bone turnover marker values and IL-6 and TGFβ1 tend to decrease with the length of the posttransplant period. A tendency towards a decrease in soluble IL-6 receptor concentration posttransplant was observed in women. Also, confirmed were positive correlations of bone turnover markers with IL-6, soluble IL-6 receptor and, in women, with TGFβ1 concentrations. In men, observed was an inversely proportionate relation of serum TNFα concentration and of bone alkaline phosphatase (a bone formation marker) activity. Confirmed was also a positive correlation between IL-6 and iPTH as well as iPTH and bone turnover marker concentrations. Proven was also a positive correlation between TGFβ1 and soluble IL-6 receptor, and, in women, of TGFβ1 and IL-6 concentrations, too. It can be postulated that the same factors partly influenced the above cytokine concentrations, too. In patients with kidney transplants there is an association of IL-6, soluble IL-6 receptor, TGFβ1, TNFα and bone turnover marker concentrations, which speaks in favour of a role of these growth factors in posttransplant bone metabolism.

Abstract in Croatian

U bolesnika nakon transplantacije bubrega i nakon uspostave dobre bubrežne funkcije prisutni su poremećaji koštanog metabolizma. Ovi su poremećaji vrlo vjerojatno posljedica poremećaja koji su nastali tijekom bolesti prije transplantacije i koji postoje i nakon transplantacije, no nakon transplantacije se pojavljuju novi čimbenici s negativnim utjecajem na koštani metabolizam (primjena imunosupresivnih lijekova). U bolesnika s dobrom i stabilnom funkcijom bubrega, neinvazivnim pokazateljima koštane pregradnje procijenjen je stupanj koštane pregradnje. U svrhu procjene stupnja koštane pregradnje određeni su sljedeći parametri u serumu/urinu bolesnika: kalcij, anorganski fosfat, iPTH, osteokalcin, prokolagen I., koštana alkalna fosfataza, deoksipiridinolinske poprečne veze. Određena je koncentracija IL-6, topljivog IL-6 receptora, TGF1, TNF u serumu, citokina, za koje je poznato da imaju ulogu u procesu koštane pregradnje. U studiju su bila uključena 64 bolesnika, u 18 je ispitivanje učinjeno tijekom prve posttransplantacijske godine, a u 46 bolesnika je posttransplantacijski period bio duži od 12 mjeseci. U 16 bolesnika, u kojih je ispitivanje bilo učinjeno tijekom prve posttransplantacijske godine, kontrolno je mjerenje bilo učinjeno u razmaku od barem 2 mjeseca. U većine je bolesnika, prema pokazateljima koštane pregradnje, koštana pregradnja bila ubrzana. Koncentracija deoksipiridinolinskih poprečnih veza bila je viša u žena nego u muškaraca. Dužina liječenja dijalizom čimbenik je rizika ubrzane koštane pregradnje nakon transplantacije bubrega. Uočena je tendencija snižavanja pokazatelja koštane pregradnje te koncentracija IL-6 i TGF1 s dužinom posttransplantacijskog perioda. Tendencija snižavanja koncentracije topljivog IL-6 receptora nakon transplantacije uočena je u žena. Pokazano je postojanje pozitivne korelacije koncentracija IL-6, topljivog IL-6 receptora, a u žena i TGF1, s pokazateljima koštane pregradnje. U muškaraca je pokazan obrnut odnos koncentracije TNF u serumu i aktivnosti koštane alkalne fosfataze, pokazatelja koštane izgradnje. Pokazano je, nadalje, postojanje pozitivne korelacije koncentracija IL-6 i iPTH, te iPTH i pokazatelja koštane pregradnje. Pokazano je postojanje pozitivne korelacije i između koncentracija TGF1 i topljivog IL-6 receptora, a u žena i koncentracija TGF1 i IL-6. Može se pretpostaviti da su u bolesnika na koncentracije navedenih citokina dijelom utjecali isti čimbenici. U bolesnika s presađenim bubregom postoji povezanost koncentracija IL-6, topljivog IL-6 receptora, TGF1, TNF i pokazatelja koštane pregradnje, a što ukazuje na ulogu ovih čimbenika rasta na koštani metabolizam nakon transplantacije bubrega.

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