Abstract | Uvod:
Imunosupresivno (IS) liječenje predstavlja rizik za oportunitističke infekcije u bolesnika s
transplantiranim bubregom. Poliomavirusna nefropatija uzrokovana BK virusom (BK virusna
nefropatija;BKVAN) kao infektivna komplikacija jedan je od značajnijih uzroka gubitka
presađenog bubrega. Cilj istraživanja bio je utvrditi klinički tijek BKVAN i ishod presatka te
osjetljivost i specifičnost citologije urina i lančane reakcije polimerazom (PCR) u dijagnostici
BKVAN.
Metode:
Provedeno je retrospektivno istraživanje na 16 bolesnika s BKVAN i 32 kontrolna bolesnika s
presađenim bubregom, bubregom i gušteračom te bubregom i jetrom. IS terapija se sastojala
od takrolimusa, mikofenolat mofetila (MMF) i steroida u 35 pacijenata, od takrolimusa i
MMF u 10, ciklosporina, MMF i steroida u 2 bolesnika, dok je jedan bolesnik primao
takrolimus, azatioprin i steroide. BKVAN je liječena visokom dozom intravenskih
imunoglobulina i/ili smanjenjem IS.
Rezultati:
Medijan vremena od transplantacije do PHD BKVAN bio je 366 (130-3065) dana. Citološki
nalaz decoy stanica u vrijeme PHD bio je pozitivan u 73.3% bolesnika s BKVAN te u 10.71%
ispitanika iz kontrolne skupine.Osjetljivost citološkog nalaza decoy stanica u urinu iznosila je
73.33% a specifičnost 89.29%. PCR za BKV DNA u plazmi bio je pozitivan u 100%
bolesnika s BKVAN i 22.22% ispitanika iz kontrolne skupine. Osjetljivost PCR testa za
BKVAN bila je 100%, a specifičnost PCR za BKVAN iznosila je 77.78%. Nakon
postavljanja PHD BKVAN ispitanici su imali medijan praćenja od 311 (32-1898) dana. Jedan
je bolesnik u tom razdoblju umro, a dvoje je izgubilo presadak. Ukupno petogodišnje
preživljenje presatka nakon postavljanja dijagnoze bilo je 65.3%. Petogodišnje preživljenje
bubrega u kontrolnoj skupini bilo je 90.6% (u usporedbi s BKVAN p=0.44, log-rank test).
Pronađena je značajna statistička razlika između promatranih skupina u vrijednosti serumskog
kreatinina 1 mjesec prije PHD (175.38}50.78 s BKVAN, 132.75}49.43 bez BKVAN, p<
0.025), u vrijeme PHD (202.13}68.51 s BKVAN, 140.09}56.14 bez BKVAN, p<0.005) i 3
mjeseca nakon PHD (221.29}108.67 s BKVAN, 134}80.43 bez BKVAN, p<0.025).
Zaključak:
BKVAN je važna infektivna komplikacija transplantacije bubrega, koja uz odgovarajući
postupak u velikom postotku bolesnika ne mora dovesti do gubitka bubrežnog presatka. PCR
za BKV DNA u plazmi i citologija urina predstavljaju važne testove probira bolesnika s
rizikom za BKVAN. |
Abstract (english) | Introduction:
Immunosuppressive therapy poses risks for increased incidence of opportunistic infections in
patients with a transplanted kidney. Being an infective complication, BK virus nephropathy
(BKVAN) is one of the leading causes of renal transplant loss. The aim of this study was to
determine the clinical course and the outcome of the graft, as well as the sensitivity and
specificity of urine cytology and polymerase chain reaction (PCR) in BKVAN diagnostics.
Methods:
A retrospective case-control study was conducted in a cohort of 48 patients with a kidney,
kidney-pancreas, and kidney-liver transplant, 16 of whom had been pathohistologically
(PHD) diagnosed with BK polyomarivus nephropathy. Immunosuppressive therapy consisted
of tacrolimus, mycrophenolate mofetil (MMF) and steroids in 35 patients, of tacrolimus and
MMF in 10 patients, and of cyclosporine, MMF and steroids in 2 patients, while one patient
was treated with tacrolimus, azathioprine and steroids. BKVAN was treated with a high dose
of intravenous immunoglobulins and/or immunosuppression reduction.
Results:
Median time between transplantation and PHD of BKVAN was 366 (130-3065) days.
Cytology test results for decoy cells at the time of PHD were positive in 73.3% of patients
with BKVAN and in 10.71% of patients from the control group of kidney transplant
recipients. PCR for BKV-DNA in plasma was positive in100%of patients with BKVAN and
in 22.22% of patients from the control group. Sensitivity of positive PCR for BKV-DNA in
plasma was 100% and specificity was 77.78%. Urine cytology for decoy cells had a
sensitivity of 73.3% and a specificity of 89.29% for BK nephropathy. Median time of patient
follow-up after the PHD of BKVAN was 311 (32-1898) days. One of the patients died during
that period, and two lost the renal graft. Overall 5-yeargraft survival rate following diagnosis
was 65.3 %, while it was 90.6% in the control group (p=0.44, log-rank test). A significant
statistical difference between the studied groups was found in serum creatinine values
measured 1 month before the PHD (202.13±68.51 with BKVAN, 140.09±56.14 without
BKVAN,p<0.025), at the time of the PHD (202.13±68.51 with BKVAN, 140.09±56.14
without BKVAN, p<0.005), and 3 months after the PHD (221.29±108.67 with BKVAN,
134±80.43 without BKVAN, p<0.025).
Conclusion:
BKVAN is an important post-kidney transplant infective complication which, if properly
treated, in a large percentage of patients will not necessarily result in transplant loss. Urine
cytology and PCR for BKV-DNA in plasma are valuable screening tests for patients at risk of
BKVAN. |