| Abstract | UVOD: Cilj istraživanja bio je ispitati povezanosti sindroma dugog COVID-a sa serumskim kalprotektinom, surogatnim markerom aktivacije neutrofila, i krutosti krvnih žila u bolesnika s transplantiranim bubregom. MATERIJALI I METODE: U presječno istraživanje slučajeva i kontrola uključeno je 98 bolesnika prosječne dobi 62 godine, 64.3% muškaraca, s funkcionalnim transplantiranim bubregom koji su preboljeli SARS-CoV-2 infekciju potvrđenu RT-PCR-om u brisu nazofarinksa. Simptomi dugog COVID-a procijenjeni su standardiziranim upitnicima kvalitete života i funkcionalnog respiracijskog kapaciteta. Krutost krvnih žila mjerena je tehnologijom oscilometrije. Serumski kalprotektin određen je turbidimetrijskom metodom. Za svakog ispitanika prikupljeni su anamnestički podatci te klinički i laboratorijski parametri iz vremena COVID-19 bolesti i longitudinalnog presjeka. REZULTATI: Poteškoće s pokretljivosti imalo je 44.3%, samostalnom brigom o sebi 6.2%, uobičajenim fizičkim aktivnostima 35.1%, bolovima/nelagodom u ekstremitetima 52.5% te anksioznosti i depresijom 26.8% ispitanika. Nije bilo razlika u simptomima sindroma dugog COVID-a s obzirom na serumski kalprotektin (p=0,12) i vrijeme proteklo od COVID-19 bolesti (p=0,09). Najsnažnija je bila povezanost sindroma dugog COVID-a s oštećenom bubrežnom funkcijom (p<0,001). Prediktori viših vrijednosti serumskog kalprotektina bili su najteži klinički fenotipovi COVID-19 bolesti (p=0,03), vremenski okviri prvih 6 mjeseci i nakon godinu dana od COVID-19 bolesti (p=0,01), kronična antihipertenzivna terapija (p=0,007), te upalni (p=0,009) i metabolički (p=0,006) laboratorijski parametri u rekonvalescenata. Povezanost serumskog kalprotektina i bubrežne funkcije obrnuto je proporcionalna (p<0,001). Osobito je zanimljiva pozitivna povezanost serumskog kalprotektina s porastom albuminurije nakon preboljenja COVID-19 bolesti (p=0,04). Serumski kalprotektin (p=0,005), laktat dehidrogenaza (p=0,03) i krutost krvnih žila (p=0,04) slijede bimodalnu longitudinalnu raspodjelu s najvišim vrijednostima u prvih 6 mjeseci i nakon godine dana od COVID-19 bolesti. ZAKLJUČAK: Sindrom dugog COVID-a češći je u bolesnika s transplantiranim bubregom nego u općoj populaciji. Nismo dokazali povezanosti sindroma dugog COVID-a sa serumskim kalprotektinom ili vremenom proteklim od COVID-19 bolesti. Sindrom dugog COVID-a i serumski kalprotektin povezani su s parametrima oštećene bubrežne funkcije ispitanika. Drugi vršak serumskog kalprotektina, laktat dehidrogenaze i krutosti krvih žila nakon godinu dana od COVID-19 bolesti može biti znak subkliničkog odbacivanja trasnplantiranog bubrega prije nego sindroma dugog COVID-a. Potrebna su daljnja randomizirana kontrolirana istraživanja serumskog kalprotektina u ulozi biomarkera subkliničkog odbacivanja bubrega, alternativnog izbora dd-cfDNA i protokolarnim biopsijama. |
| Abstract (english) | INTRODUCTION: The aim of this study was to investigate long COVID symptoms, serum calprotectin levels as a surrogate for neutrophil activation, arterial stiffness parameters and their possible correlations in kidney transplant recipients. MATERIALS AND METHODS: A cross-sectional and case-control study was conducted in 98 kidney transplant recipients with a mean age of 62 years and 64.3% men with functioning grafts who had recovered from SARS-CoV-2 infection detected by RT-PCR in naspharingeal swabs. Long COVID symptoms were assessed with standardized quality of life questionnaires. Arterial stiffness was measured by oscillometry. Serum calprotectin was measured using a particle-enhanced turbidimetric immunoassay. The medical history, clinical and laboratory parameters of COVID-19 disease and long-term follow-up were recorded for each study participant. RESULTS: Of 98 kidney transplant recipients with an average age of 62 years, 64.3% were men. There were difficulties with mobility in 44.3%, with self-care in 6.2%, with usual activities in 35.1%, with pain in the extremities in 52.5%, and with anxiety and depression in 26.8% of those examined. No differences were found in long COVID symptoms with respect to serum calprotectin levels (p=0.12) and time elapsed since COVID-19 (p=0.09). The association of long COVID symptoms was strongest with impaired renal function (p=<0.001). Predictors of higher serum calprotectin levels were the most severe clinical phenotypes of COVID-19 disease (p=0.03), periods of the first 6 months and beyond one year of COVID-19 disease (p=0.01), chronic antihypertensive therapy (p=0.007) and proinflammatory (p=0.009) and metabolic (p=0.006) laboratory parameters of convalescents. The relationship between serum calprotectin and renal function parameters was inverse (p=<0.001). Most interesting was the relationship between serum calprotectin and the change in albuminuria after COVID-19 disease (p=0.04). Serum calprotectin (p=0.005), lactate dehydrogenase (p=0.03) and arterial stiffness (p=0.04) followed a bimodal longitudinal distribution with the highest values in the first 6 months and after 12 months of COVID-19 disease. CONCLUSION: Long COVID syndrome is more common in kidney transplant recipients than in the general population. There were no correlations between long COVID syndrome and serum calprotectin levels or time elapsed since COVID-19 disease. Both long COVID syndrome and serum calprotectin are associated with impaired renal function parameters in the subjects. The second peak values of serum calprotectin, lactate dehydrogenase and arterial stiffness one year after COVID-19 disease could be a marker for subclinical rejection rather than long COVID syndrome. Further randomised controlled trials using serum calprotectin as a surrogate for subclinical rejection as an alternative screening to dd-cfDNA and protocol biopsies, are needed. |
