Pomen puste telesne mase pri oceni hitrosti glomerulne filtracije pri bolnikih s presajeno ledvico

Borštnar, Špela (avtor), Kovač, Damjan (mentor)

Izhodišča. Pri bolnikih po presaditvi ledvice je pomembno čim bolj natančno oceniti delovanje presadka. Od tega so odvisni različni diagnostični in terapevtski postopki, odmerjanje zdravil, ki se izločajo skozi ledvice, in odločitev, kdaj je treba pričeti z nadomestnim zdravljenjem. Uporaba najpogosteje uporabljenih in priporočenih enačb za oceno glomerulne filtracije (oGF) ni vedno zanesljiva, še posebej ne v posebnih populacijah, kot so bolniki s presajeno ledvico. Bolniki po presaditvi ledvice prejemajo imunosupresivna zdravila, soočajo se z različnimi novo nastalimi bolezenskimi stanji in so nagnjeni k okužbam. Vsa ta stanja vplivajo na spremenjeno sestavo telesa. Kljub velikemu vplivu mišične mase na serumsko koncentracijo kreatinina (s-kreatinin) nobena izmed priporočenih enačb za oGF ne upošteva mišične mase. Z raziskavo smo želeli preveriti dve hipotezi, in sicer da so do sedaj najbolj uveljavljene enačbe za oGF pri bolnikih s presajeno ledvico nezanesljive ter da je pri bolnikih s presajeno ledvico suha pusta telesna masa pomemben dejavnik pri oGF in da z upoštevanjem le-te bolje ocenimo glomerulno filtracijo (GF). Želeli smo tudi ugotoviti, ali se zanesljivost posameznih enačb spreminja s stopnjo ledvične okvare in s preračunavanjem rezultata na telesno površino 1,73 m2, ter podati novo enačbo za oGF pri bolnikih s presajeno ledvico, ki bi upoštevala suho pusto telesno maso in bila zanesljivejša od obstoječih enačb. Metode. V prospektivno klinično raziskavo smo vključili 100 bolnikov s presajeno ledvico. Vsem preiskovancem smo ob pregledu izmerili telesno težo in višino, izračunali smo indeks telesne mase in telesno površino. Izmerili smo jim debelino kožnih gub in obsege določenih delov telesa. Z bioimpendančno analizo smo jim izmerili telesno sestavo, pusto telesno maso (maso telesa brez maščevja) in suho pusto telesno maso (pusto telesno maso brez telesne vode), ki odražata predvsem maso mišičja. Izračunali smo korigiran očistek kreatinina iz 24-urnega urina (korOkr) in s Cockcroft-Gaultovo enačbo (korOkr CG). Glomerulno filtracijo smo ocenili s pomočjo poenostavljene in revidirane enačbe raziskave »Modification of Diet in Renal Disease« (oGF MDRD), z enačbo epidemiološke raziskave o kronični ledvični bolezni, ki upošteva s-kreatinin (oGF CKD-EPIkr), serumsko koncentracijo cistatina c (s-cistatin C) (oGF CKD-EPIcis) in obe s-kreatinin in s-cistatin C (oGF CKD-EPIkr-cis), z enostavno (oGFeno-cis) ter z »mariborsko« enačbo s s-cistatinom C (oGFmar- cis). Istočasno smo jim izmerili očistek 51krom-etilendiamintetraocetne kisline (korGF 51Cr-EDTA) in ga primerjali z naštetimi pokazatelji GF. Na podlagi korGF 51Cr-EDTA smo preiskovance razdelili v pet skupin in primerjali rezultate med skupinami. Izračunali smo zanesljivost posameznih pokazateljev GF in povezanost parametrov telesne sestave ter antropometričnih meritev s korGF 51Cr-EDTA. Rezultati. Od 100 preiskovancev je bilo 53 moških in 47 žensk. Povprečna starost je bila 56 ± 11 let (od 27 do 79 let). Povprečen čas od presaditve je bil 10 ± 6 let (od 2 do 28 let). 75 % preiskovancev je imelo znižan delež, 19 % je imelo normalen delež in le 6 % zvišan delež puste telesne mase, kot bi pričakovali glede na njihovo starost in spol. Povprečna korGF 51Cr-EDTA je bila 46,5 ± 24,5 ml/min/1,73 m2. Vse enačbe za oGF kot tudi korOkr in korOkr CG so statistično značilno precenile korGF 51Cr-EDTA (prikazano kot sistematična napaka – pristranost ± standardna deviacija (SD), ki je merilo natančnosti v ml/min/1,73 m2, s 30-odstotno točnostjo v oklepajih): korOkr 17,2 ± 16,6 (53 %), korOkr CG 16,8 ± 14,1 (44 %), oGF MDRD 12,5 ± 15,3 (54 %), oGF CKD-EPIkr 15,1 ± 15,3 (50 %), oGF CKD-EPIcis 8,0 ± 16,6 (56 %), oGF CKD-EPIkr-cis 10,3 ± 13,4 (55 %), oGFeno-cis 29,9 ± 18,8 (21 %) in oGFmar- cis 20,4 ± 19,5 (41 %). Analiza rezultatov med skupinami 1 do 5 je pokazala, da pri preiskovancih s korGF 51Cr-EDTA nad 90,0 ml/min/1,73 m2 enačbe sicer precenijo dejansko GF, vendar je bila večina enačb dovolj zanesljivih, saj je bila pristranost statistično značilna le pri korOkr CG, oGFeno-cis in oGFmar-cis. Pri korGF 51Cr-EDTA med 60,0 in 89,0 ml/min/1,73 m2 je bila zanesljiva samo oGF CKD-EPIcis, njena pristranost ni bila statistično značilna, tudi SD je bila nizka, in sicer 2,8 ± 2,9. Pri korGF 51Cr-EDTA pod 60,0 ml/min/1,73 m2 so bile vse enačbe nezanesljive, z visokimi pristranostmi, visokimi SD in nizko točnostjo. Podobno so bile enačbe nezanesljive, če nismo rezultata preračunali na standardno telesno površino 1,73 m2. Z analizo s Pearsonovim korelacijskim koeficientom smo ugotovili statistično značilno korelacijo med suho pusto telesno maso in korGF 51Cr-EDTA ter med suho pusto telesno maso in vsemi pristranostmi razen s pristranostjo oGF CKD-EPIcis. Nižja kot je bila suha pusta telesna masa, višje so bile pristranosti oz. bolj so oGF precenjevale dejansko GF. Ni bilo prisotne značilne korelacije med suho pusto telesno maso in vsemi oGF in očistkoma kreatinina. Z upoštevanjem suhe puste telesne mase in obstoječih enačb CKD-EPIkr in CKD-EPIkr-cis smo podali novi enačbi za oGF, katerih pristranost je bila nižja kot pri ostalih pokazateljih GF (–1,43 ± 13,6 ml/min/1,73 m2 in –1,64 ± 13,4 ml/min/1,73 m2). Zaključek. Z raziskavo smo potrdili hipotezo, da so enačbe za oGF in očistka kreatinina pri bolnikih s presajeno ledvico nezanesljive, saj sistematično statistično značilno precenijo izmerjeno GF. Večina enačb je sicer dovolj zanesljivih v skupini preiskovancev z dejansko GF nad 90,0 ml/min/1,73 m2, pri izmerjeni GF med 60,0 in 89,0 ml/min/1,73 m2 je bila zanesljiva samo enačba CKD-EPIcis. Pri nižjih stopnjah GF so bile vse enačbe nezanesljive. Razlog za sistematično precenjevanje enačb za oGF in očistka kreatinina je pomanjkanje puste telesne mase, saj je večina naših preiskovancev imela nižji delež puste telesne mase, kot bi pričakovali glede na njihovo starost in spol. Izkazalo se je, da je s korGF 51Cr-EDTA najbolje korelirala suha pusta telesna masa. Podali smo dve novi enačbi za oGF, ki upoštevata suho pusto telesno maso, ki sta se izkazali za zanesljivejši od obstoječih enačb za oGF in bosta tako omogočili boljšo obravnavo bolnikov po presaditvi ledvice.

• Jezik: Slovenski jezik
• Ključne besede: pusta telesna masa, suha pusta telesna masa, ocena glomerulne filtracije, bolniki s presajeno ledvico
• Vrsta gradiva: Doktorsko delo/naloga
• Organizacija: MF - Medicinska fakulteta
• Leto izida: 2022
• PID: 20.500.12556/RUL-135939
• COBISS.SI-ID: 102865923
• Datum objave v RUL: 03.04.2022

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Role of lean body mass for estimation of glomerular filtration rate in patients after kidney transplantation

Izvleček

Introduction. Evaluation of kidney function after kidney transplantation is important to determine graft function, need for diagnostic and therapeutic procedures, dosing of medicines which are excreted from the kidney and decision when to start renal replacement therapy. The use of most commonly used and recommended equations for estimation of glomerular filtration rate (eGFR) is not always reliable, especially in special populations such as patients with a kidney transplant. Renal transplant patients receive immunosuppressive therapy; they are faced with a variety of emerging diseases and are prone to many infections. All these conditions may change body composition. Despite significant influence of muscle mass on serum creatinine concentration (s-creatinine), none of the recommended equations for eGFR does not take into account muscle mass. Our study wanted to verify the hypothesis that: 1. equations for eGFR are unreliable in patients with kidney transplant, 2. dry lean body mass is an important factor in assessing glomerular filtration rate (GFR) in patients with kidney transplant and that we can better estimate GFR with considering dry lean body mass. We wanted to know if reliability of eGFR varies with different stages of renal impairment and with calculation of the result on standard body surface area 1.73 m2. The aim was to give a new equation for eGFR, which will take into consideration dry lean body mass and be more realiable than previos equations. Methods. In a prospective clinical study 100 patients with functioning kidney transplant were included. All subjects had measured body weight and height; we calculated the body mass index and body surface area. We measured them the thickness of skin folds and circumference of certain parts of the body. Body composition was measured with bioimpedance analysis to determine lean body mass (body mass without fat mass) and dry lean body mass (lean body mass without body water), both reflect the patient’s muscle mass. We calculated creatinine clearance from 24-hour urine (CrCl) and using the Cockcroft-Gault equation (ClCr CG). GFR was estimated with simplified and revised Modification of Diet in Renal Disease equation (eGFR MDRD), with Chronic Kidney Disease Epidemiology Collaboration equation with s-creatinine (eGFR CKD-EPICr), serum cystatin C concentration (s-cystatin C) (eGFR CKD-EPICysC) and with s-creatinine and s-cystatine C (eGFR CKD-EPICr-CysC), with simple (eGFRCys), and with the "Maribor" equation with s-cystatin C (eGFRmar-Cys). On the same day we determined clearance of 51chromium-ethylenediaminetetraacetic acid (mGFR 51Cr-EDTA) and compared it with listed indicators of GFR. Patients were distributed according to mGFR 51Cr-EDTA into 5 groups. We identified the reliability of individual GFR indicators and the correlations of body composition parameters and anthropometric measurements with mGFR 51Cr-EDTA. Results. Of the 100 patients there were 53 men and 47 women. The average age was 56 ± 11 years (from 27 to 79 years). The average time from transplantation was 10 ± 6 years (from 2 to 28 years). Body composition analysis showed a reduced proportion of lean body mass in 75% of patients, 19% had normal proportion and only 6% of them increased proportion of lean body mass as compared to what would be expected according to their age and sex. The average mGFR 51Cr-EDTA was 46.5 ± 24.5 ml/min/1.73 m2. All eGFR equations as well CrCl and CrCl CG overestimated the exact GFR as measured by 51Cr-EDTA clearance by a significant degree (shown as bias ± standard deviation (SD) in ml/min/1.73 m2 with 30% accuracy in brackets): CrCl 17.2 ± 16.6 (53%), CrCl CG 16.8 ± 14.1 (44%), eGFR MDRD 12.5 ± 15.3 (54%), eGFR CKD-EPICr 15.1 ± 15.3 (50%), eGFR CKD-EPICysC 8.0 ± 16.6 (56%), eGFR CKD-EPICr-CysC 10.3 ± 13.4 (55%), eGFRCys 29.9 ± 18.8 (21%) and eGFRmar-Cys 20.4 ± 19.5 (41%). Analysis of the results between the groups 1-5 showed that in patients with mGFR 51Cr-EDTA over 90.0 ml/min/1.73 m2 equations overestimated the actual GFR, but most of the equations were sufficiently reliable, the bias reached statistically significant difference only in the CrCl CG, eGFRCys and eGFRmar-Cys. When mGFR 51Cr-EDTA was between 60.0 to 89.0 ml/min/1.73 m2, only eGFR CKD-EPICysC was reliable with low bias and low SD: 2.8 ± 2.9 (68%). When mGFR 51Cr-EDTA was below 60.0 ml/min/1.73 m2 all equations were unreliable with high bias, high SD and low accuracy. Similarly, the equations were unreliable, if the results were not calculated to standard body surface 1.73 m2. Analysis with the Pearson’s correlation coefficient showed statistically significant correlation between dry lean body mass and mGFR 51Cr-EDTA and between dry lean body mass and all biases except with eGFR CKD-EPICysC’s bias. The lower was the dry lean body mass, the higher was overestimation of actual GFR. There was no correlation between dry lean body mass and any of the eGFRs and creatinine clearances. We developed two new equations for eGFR with the dry lean body mass and existing equations CKD-EPICr and CKD-EPICr-CysC, their bias was lower than in other indicators of GFR (-1.43 ± 13.6 ml/min/1.73 m2 and - 1.64 ± 13.4 ml/min/1.73 m2). Conclusions. We have proven that the most widely used equation for eGFR and creatinine clearance are unreliable in patients with kidney transplant as they systematically overestimate actual GFR. Most of the equations were sufficiently reliable in actual GFR over 90.0 ml/min/1.73 m2. When actual GFR was between 60.0 to 89.0 ml/min/1.73 m2, only eGFR CKD-EPICysC was sufficiently reliable. At lower levels of GFR all equations were unreliable. The reason for the systematic overestimation of eGFR equations and creatinine clearances is the lack of lean body mass, as the majority of our patients had decreased lean body mass. It turns out that dry lean body mass had the best correlation with mGFR 51Cr-EDTA. We developed two new equations for eGFR with dry lean body mass, which proved to be more reliable than the existing equations for eGFR and will allow us better managment of renal transplant patients.

• Ključne besede: lean body mass, dry lean body mass, estimation of glomerular filtration rate, renal transplant patiens