INFECTION IN DIALYSIS AND AFTER KIDNEY TRANSPLANTATION

Nadomještanjem bubrežne funkcije u Hrvatskoj se liječi gotovo 4500 bolesnika. Česte infekcije u populaciji liječenoj dijalizom i transplantacijom bubrega jedan su od najčešći uzrok moribiditeta i mortaliteta tih bolesnika. U bolesnika liječenih dijalizom infekcije su uobičajeno vezane uz dijalizni pristup (najčešće dijalizni centralni venski, ili peritonejski kateter). U bolesnika s transplantiranim bubregom infekcije se najčešće javljaju u ranom poslijeoperativnom razdoblju. Prevencija, rano prepoznavanje i adekvatno liječenje infekcija u toj populaciji ključni su za bolje preživljenje ovih bolesnika s kojima se sve češće susreću i liječnici drugih specijalnosti.Almost 4500 patients are being treated with renal replacement therapies in Croatia. Infections are frequent in the population treated with dialysis and kidney transplantation, being one of the most common causes of morbidity and mortality in these patients. In dialysis patients, infections are usually related to dialysis access (usually central venous dialysis catheter or peritoneal catheter). In kidney transplant recipients, infections are most common in the early postoperative period. Prevention, early recognition, as well as appropriate treatment of infection are all crucial for better survival of these patients, with ever more other medical specialties being involved in their management

Urine Immunocytology as a Noninvasive Diagnostic Tool for Acute Kidney Rejection: a Single Center Experience

Renal biopsy is a gold standard for establishing diagnosis of acute rejection of the renal allograft. However, being invasive, renal biopsy has potential significant complications and contraindications. Therefore, possibility to noninvasively diagnose acute rejection would improve follow-up of kidney transplant patients. The purpose of this study was to evaluate urine immunocytology for T cells as a method for noninvasive identification of patients with acute renal allograft rejection in comparison to renal biopsy. In this prospective study a cohort of 56 kidney, or kidney-pancreas transplant recipients was included. Patients either received their transplant at the University Hospital »Merkur«, or have been followed at the »Merkur« Hospital. Patients were subject to either protocol or indication kidney biopsy (a total of 70 biopsies), with simultaneous urine immunocytology (determination of CD3-positive cells in the urine sediment). Acute rejection was diagnosed in 24 biopsies. 23 episodes were T-cell mediated (6 grade IA, 5 grade IB, 1 grade IIA, 1 grade III and 10 borderline), while in 1 case acute humoral rejection was diagnosed. 46 biopsies did not demonstrate acute rejection. CD3-positive cells were found in 21% of cases with acute rejection and in 13% of cases without rejection (n.s.). A finding of CD3-positive cells in urine had a sensitivity of 21% and specificity of 87% for acute rejection (including borderline), with positive predictive value of 45% and negative predictive value of 68%. Although tubulitis is a hallmark of acute T cell-mediated rejection, detection of T cells in urine sediment was insufficiently sensitive and insufficiently specific for diagnosing acute rejection in our cohort of kidney transplant recipients

Tunnelled haemodialysis catheter and haemodialysis outcomes: a retrospective cohort study in Zagreb, Croatia

OBJECTIVES: Studies have reported that the tunnelled dialysis catheter (TDC) is associated with inferior haemodialysis (HD) patient survival, in comparison with arteriovenous fistula (AVF). Since many cofactors may also affect survival of HD patients, it is unclear whether the greater risk for survival arises from TDC per se, or from associated conditions. Therefore, the aim of this study was to determine, in a multivariate analysis, the long-term outcome of HD patients, with respect to vascular access (VA). ----- DESIGN: Retrospective cohort study. ----- PARTICIPANTS: This retrospective cohort study included all 156 patients with a TDC admitted at University Hospital Merkur, from 2010 to 2012. The control group consisted of 97 patients dialysed via AVF. The groups were matched according to dialysis unit and time of VA placement. The site of choice for the placement of the TDC was the right jugular vein. Kaplan-Meier analysis with log-rank test was used to assess patient survival. Multivariate Cox regression analysis was used to determine independent variables associated with patient survival. ----- PRIMARY OUTCOME MEASURES: Patient survival with respect to VA. ----- RESULTS: The cumulative 1-year survival of patients who were dialysed exclusively via TDC was 86.4% and of those who were dialysed exclusively via AVF, survival was 97.1% (p=0.002). In multivariate Cox regression analysis, male sex and older age were independently negatively associated with the survival of HD patients, while shorter HD vintage before the creation of the observed VA, hypertensive renal disease and glomerulonephritis were positively associated with survival. TDC was an independent risk factor for survival of HD patients (HR 23.0, 95% CI 6.2 to 85.3). ----- CONCLUSION: TDC may be an independent negative risk factor for HD patient survival

Impact of early steroid withdrawal on progression of interstitial fibrosis and tubular atrophy after kidney transplantation

Uvod: Utjecaj ranoga ukidanja steroida na progresiju kroničnih patohistoloških promjena nakon transplantacije bubrega nije sasvim razjašnjen. Cilj studije je bio utvrditi utjecaj ranoga ukidanja steroida nakon transplantacije bubrega na progresiju IF/TA-e. Nadalje, analizirana je pojavnost subkliničke upale i akutnih te subkliničkih akutnih odbacivanja između skupina imunosupresije s ranim ukidanjem steroida i onima koji su steroide imali kontinuirano u imunosupresiji održavanja. 1. i 5. god. preživljenje bolesnika i presatka analizirano je među navedenim skupinama imunosupresije. Epitelno-mezenhimalna tranzicija (EMT) kao eventualni prediktor nastanka IF/TA-e analizirana je u protokol biopsijama 1. i 3. mj. od transplantacije. ----- Ispitanici i metode: U istraživanje su uključena 124 bolesnika s transplantiranim bubregom i simultano bubregom i gušteračom. Uključeni su bolesnici s niskim imunološkim rizikom bez odgođene funkcije presatka. U 79 bolesnika steroidi su ukidani peti dan od transplantacije a 45 bolesnika imalo je steroide kontinuirano u imunosupresiji održavanja uz kalcineurinski inhibitor i MMF. U indukcijskoj imunosupresiji korišteno je protutijelo na IL-2 receptor. Protokol biopsije bubrega su rađene pri implantaciji i 12 mj. od transplantacije. Progresija skorova (delta) tijekom prve godine od transplantacije dobivena je oduzimanjem kroničnih skorova na nultoj biopsiji od kroničnih skorova na 12 mj. od transplantacije. Skor totalne upale (ti) analiziran je na 12 mj. biopsijama. Vrijednosti skorova su 0 – 3. Za vrednovanje kroničnih patohistoloških promjena korištena je Banff 97 i Banff 07 klasifikacija. EMT je učinjen simultanim bojenjem na α glatki mišić i E kadherin na protokol biopsijama 1 i 3 mj. od transplantacije. ----- Rezultati: Između skupina imunosupresije s ranim ukidanjem steroida i na steroidima nema statistički značajne razlike u progresiji intersticijske fibroze (0.52 ± 0.62 vs. 0.69 ± 0.76, p=0.28) i tubularne atrofije (0.58 ± 0.67 vs. 0.76 ± 0.71, p=0.17). Nije bilo statistički značajne razlike u ti skoru na biopsijama bubrega 12 mj. nakon transplantacije među pojedinim skupinama imunosupresije s ranim ukidanjem steroida i na steroidima (0.54±0.86 vs. 0.67±0.79, p=0.23). Nema razlike među grupama imunosupresije sa i bez steroida u preživljenju bolesnika i presatka 1. i 5. god. nakon transplantacije te incidenciji akutnih i subkliničkih odbacivanja u 1. god. nakon transplantacije bubrega. Bubrežna funkcija u svim vremenskim intervalima (3, 6 i 12 mj., 3 i 5 god.) nakon transplantacije bila je bez statistički značajne razlike među skupinama. EMT nije detektiran na uzorcima protokol biopsija bubrega. ----- Zaključak: Rano ukidanje steroida nakon transplantacije bubrega nema utjecaja na progresiju kroničnih patohistoloških skorova u 1. god. nakon transplantacije bubrega.Introduction: Long-term effects of early steroid withdrawal (ESW) on development of chronic pathophysiology changes in kidney allograft is unclear. ----- Methods: In this study we compared chronic scores on protocol biopsies in Caucasian kidney recipients (N=124) without DGF with ESW (79) vs. continuous steroids (45) on top of CNI and MMF. Induction consisted of IL-2R antibody. Protocol biopsies were done on day 0 and 1 year after transplant. Chronic scores (ci, ct, cg, mm, cv and ah) were analyzed by Banff' 97 and its update Banff 07 classification. Total inflammation (ti) score was analyzed on protocol biopsies 1 year after transplantation. ----- Results: Progression of interstitial fibrosis was in ESW (0.52 ± 0.62 vs. 0.69 ± 0.76, p=0.28) and in tubular atrophy (0.58 ± 0.67 vs. 0.76 ± 0.71, p=0.17) versus continuous steroids group. ti score on protocol kidney biopsies 12 months after transplantation was in ESW (0.54±0.86 vs. 0.67±0.79, p=0.23) versus continuous steroids group. ----- Conclusion: In conclusion, ESW does not have impact on progression of IF/TA. ti score was comparable between ESW and continuous steroids group on 12 months protocol transplant biopsies

Impact of early steroid withdrawal on progression of interstitial fibrosis and tubular atrophy after kidney transplantation

Uvod: Utjecaj ranoga ukidanja steroida na progresiju kroničnih patohistoloških promjena nakon transplantacije bubrega nije sasvim razjašnjen. Cilj studije je bio utvrditi utjecaj ranoga ukidanja steroida nakon transplantacije bubrega na progresiju IF/TA-e. Nadalje, analizirana je pojavnost subkliničke upale i akutnih te subkliničkih akutnih odbacivanja između skupina imunosupresije s ranim ukidanjem steroida i onima koji su steroide imali kontinuirano u imunosupresiji održavanja. 1. i 5. god. preživljenje bolesnika i presatka analizirano je među navedenim skupinama imunosupresije. Epitelno-mezenhimalna tranzicija (EMT) kao eventualni prediktor nastanka IF/TA-e analizirana je u protokol biopsijama 1. i 3. mj. od transplantacije. ----- Ispitanici i metode: U istraživanje su uključena 124 bolesnika s transplantiranim bubregom i simultano bubregom i gušteračom. Uključeni su bolesnici s niskim imunološkim rizikom bez odgođene funkcije presatka. U 79 bolesnika steroidi su ukidani peti dan od transplantacije a 45 bolesnika imalo je steroide kontinuirano u imunosupresiji održavanja uz kalcineurinski inhibitor i MMF. U indukcijskoj imunosupresiji korišteno je protutijelo na IL-2 receptor. Protokol biopsije bubrega su rađene pri implantaciji i 12 mj. od transplantacije. Progresija skorova (delta) tijekom prve godine od transplantacije dobivena je oduzimanjem kroničnih skorova na nultoj biopsiji od kroničnih skorova na 12 mj. od transplantacije. Skor totalne upale (ti) analiziran je na 12 mj. biopsijama. Vrijednosti skorova su 0 – 3. Za vrednovanje kroničnih patohistoloških promjena korištena je Banff 97 i Banff 07 klasifikacija. EMT je učinjen simultanim bojenjem na α glatki mišić i E kadherin na protokol biopsijama 1 i 3 mj. od transplantacije. ----- Rezultati: Između skupina imunosupresije s ranim ukidanjem steroida i na steroidima nema statistički značajne razlike u progresiji intersticijske fibroze (0.52 ± 0.62 vs. 0.69 ± 0.76, p=0.28) i tubularne atrofije (0.58 ± 0.67 vs. 0.76 ± 0.71, p=0.17). Nije bilo statistički značajne razlike u ti skoru na biopsijama bubrega 12 mj. nakon transplantacije među pojedinim skupinama imunosupresije s ranim ukidanjem steroida i na steroidima (0.54±0.86 vs. 0.67±0.79, p=0.23). Nema razlike među grupama imunosupresije sa i bez steroida u preživljenju bolesnika i presatka 1. i 5. god. nakon transplantacije te incidenciji akutnih i subkliničkih odbacivanja u 1. god. nakon transplantacije bubrega. Bubrežna funkcija u svim vremenskim intervalima (3, 6 i 12 mj., 3 i 5 god.) nakon transplantacije bila je bez statistički značajne razlike među skupinama. EMT nije detektiran na uzorcima protokol biopsija bubrega. ----- Zaključak: Rano ukidanje steroida nakon transplantacije bubrega nema utjecaja na progresiju kroničnih patohistoloških skorova u 1. god. nakon transplantacije bubrega.Introduction: Long-term effects of early steroid withdrawal (ESW) on development of chronic pathophysiology changes in kidney allograft is unclear. ----- Methods: In this study we compared chronic scores on protocol biopsies in Caucasian kidney recipients (N=124) without DGF with ESW (79) vs. continuous steroids (45) on top of CNI and MMF. Induction consisted of IL-2R antibody. Protocol biopsies were done on day 0 and 1 year after transplant. Chronic scores (ci, ct, cg, mm, cv and ah) were analyzed by Banff' 97 and its update Banff 07 classification. Total inflammation (ti) score was analyzed on protocol biopsies 1 year after transplantation. ----- Results: Progression of interstitial fibrosis was in ESW (0.52 ± 0.62 vs. 0.69 ± 0.76, p=0.28) and in tubular atrophy (0.58 ± 0.67 vs. 0.76 ± 0.71, p=0.17) versus continuous steroids group. ti score on protocol kidney biopsies 12 months after transplantation was in ESW (0.54±0.86 vs. 0.67±0.79, p=0.23) versus continuous steroids group. ----- Conclusion: In conclusion, ESW does not have impact on progression of IF/TA. ti score was comparable between ESW and continuous steroids group on 12 months protocol transplant biopsies

Impact of early steroid withdrawal on progression of interstitial fibrosis and tubular atrophy after kidney transplantation

Uvod: Utjecaj ranoga ukidanja steroida na progresiju kroničnih patohistoloških promjena nakon transplantacije bubrega nije sasvim razjašnjen. Cilj studije je bio utvrditi utjecaj ranoga ukidanja steroida nakon transplantacije bubrega na progresiju IF/TA-e. Nadalje, analizirana je pojavnost subkliničke upale i akutnih te subkliničkih akutnih odbacivanja između skupina imunosupresije s ranim ukidanjem steroida i onima koji su steroide imali kontinuirano u imunosupresiji održavanja. 1. i 5. god. preživljenje bolesnika i presatka analizirano je među navedenim skupinama imunosupresije. Epitelno-mezenhimalna tranzicija (EMT) kao eventualni prediktor nastanka IF/TA-e analizirana je u protokol biopsijama 1. i 3. mj. od transplantacije. ----- Ispitanici i metode: U istraživanje su uključena 124 bolesnika s transplantiranim bubregom i simultano bubregom i gušteračom. Uključeni su bolesnici s niskim imunološkim rizikom bez odgođene funkcije presatka. U 79 bolesnika steroidi su ukidani peti dan od transplantacije a 45 bolesnika imalo je steroide kontinuirano u imunosupresiji održavanja uz kalcineurinski inhibitor i MMF. U indukcijskoj imunosupresiji korišteno je protutijelo na IL-2 receptor. Protokol biopsije bubrega su rađene pri implantaciji i 12 mj. od transplantacije. Progresija skorova (delta) tijekom prve godine od transplantacije dobivena je oduzimanjem kroničnih skorova na nultoj biopsiji od kroničnih skorova na 12 mj. od transplantacije. Skor totalne upale (ti) analiziran je na 12 mj. biopsijama. Vrijednosti skorova su 0 – 3. Za vrednovanje kroničnih patohistoloških promjena korištena je Banff 97 i Banff 07 klasifikacija. EMT je učinjen simultanim bojenjem na α glatki mišić i E kadherin na protokol biopsijama 1 i 3 mj. od transplantacije. ----- Rezultati: Između skupina imunosupresije s ranim ukidanjem steroida i na steroidima nema statistički značajne razlike u progresiji intersticijske fibroze (0.52 ± 0.62 vs. 0.69 ± 0.76, p=0.28) i tubularne atrofije (0.58 ± 0.67 vs. 0.76 ± 0.71, p=0.17). Nije bilo statistički značajne razlike u ti skoru na biopsijama bubrega 12 mj. nakon transplantacije među pojedinim skupinama imunosupresije s ranim ukidanjem steroida i na steroidima (0.54±0.86 vs. 0.67±0.79, p=0.23). Nema razlike među grupama imunosupresije sa i bez steroida u preživljenju bolesnika i presatka 1. i 5. god. nakon transplantacije te incidenciji akutnih i subkliničkih odbacivanja u 1. god. nakon transplantacije bubrega. Bubrežna funkcija u svim vremenskim intervalima (3, 6 i 12 mj., 3 i 5 god.) nakon transplantacije bila je bez statistički značajne razlike među skupinama. EMT nije detektiran na uzorcima protokol biopsija bubrega. ----- Zaključak: Rano ukidanje steroida nakon transplantacije bubrega nema utjecaja na progresiju kroničnih patohistoloških skorova u 1. god. nakon transplantacije bubrega.Introduction: Long-term effects of early steroid withdrawal (ESW) on development of chronic pathophysiology changes in kidney allograft is unclear. ----- Methods: In this study we compared chronic scores on protocol biopsies in Caucasian kidney recipients (N=124) without DGF with ESW (79) vs. continuous steroids (45) on top of CNI and MMF. Induction consisted of IL-2R antibody. Protocol biopsies were done on day 0 and 1 year after transplant. Chronic scores (ci, ct, cg, mm, cv and ah) were analyzed by Banff' 97 and its update Banff 07 classification. Total inflammation (ti) score was analyzed on protocol biopsies 1 year after transplantation. ----- Results: Progression of interstitial fibrosis was in ESW (0.52 ± 0.62 vs. 0.69 ± 0.76, p=0.28) and in tubular atrophy (0.58 ± 0.67 vs. 0.76 ± 0.71, p=0.17) versus continuous steroids group. ti score on protocol kidney biopsies 12 months after transplantation was in ESW (0.54±0.86 vs. 0.67±0.79, p=0.23) versus continuous steroids group. ----- Conclusion: In conclusion, ESW does not have impact on progression of IF/TA. ti score was comparable between ESW and continuous steroids group on 12 months protocol transplant biopsies

Urine immunocytology as a noninvasive diagnostic tool for acute kidney rejection: a single center experience [Imunocitologija urina kao neinvazivni dijagnostički postupak za otkrivanje akutnog odbacivanja bubrega: iskustvo KB »Merkur«]

Renal biopsy is a gold standard for establishing diagnosis of acute rejection of the renal allograft. However, being invasive, renal biopsy has potential significant complications and contraindications. Therefore, possibility to noninvasively diagnose acute rejection would improve follow-up of kidney transplant patients. The purpose of this study was to evaluate urine immunocytology for T cells as a method for noninvasive identification of patients with acute renal allograft rejection in comparison to renal biopsy. In this prospective study a cohort of 56 kidney, or kidney-pancreas transplant recipients was included. Patients either received their transplant at the University Hospital »Merkur«, or have been followed at the »Merkur« Hospital. Patients were subject to either protocol or indication kidney biopsy (a total of 70 biopsies), with simultaneous urine immunocytology (determination of CD3-positive cells in the urine sediment). Acute rejection was diagnosed in 24 biopsies. 23 episodes were T-cell mediated (6 grade IA, 5 grade IB, 1 grade IIA, 1 grade III and 10 borderline), while in 1 case acute humoral rejection was diagnosed. 46 biopsies did not demonstrate acute rejection. CD3-positive cells were found in 21% of cases with acute rejection and in 13% of cases without rejection (n.s.). A finding of CD3-positive cells in urine had a sensitivity of 21% and specificity of 87% for acute rejection (including borderline), with positive predictive value of 45% and negative predictive value of 68%. Although tubulitis is a hallmark of acute T cell-mediated rejection, detection of T cells in urine sediment was insufficiently sensitive and insufficiently specific for diagnosing acute rejection in our cohort of kidney transplant recipients

Effect of mycophenolate mofetil on progression of interstitial fibrosis and tubular atrophy after kidney transplantation: a retrospective study

OBJECTIVES: Chronic transplant dysfunction after kidney transplantation is a major reason of kidney graft loss and is caused by immunological and non-immunological factors. There is evidence that mycophenolate mofetil (MMF) may exert a positive effect on renal damage in addition to immunosuppression, by its direct antifibrotic properties. The aim of our study was to retrospectively investigate the role of MMF doses on progression of chronic allograft dysfunction and fibrosis and tubular atrophy (IF/TA). ----- SETTING: Retrospective, cohort study. ----- PARTICIPANTS: Patients with kidney transplant in a tertiary care institution. This is a retrospective cohort study that included 79 patients with kidney and kidney-pancreas transplantation. Immunosuppression consisted of anti-interleukin 2 antibody induction, MMF, a calcineurin inhibitor±steroids. ----- PRIMARY OUTCOME MEASURES: An association of average MMF doses over 1 year post-transplant with progression of interstitial fibrosis (Δci), tubular atrophy (Δct) and estimated-creatinine clearance (eCrcl) at 1 year post-transplant was evaluated using univariate and multivariate analyses. ----- RESULTS: A higher average MMF dose was significantly independently associated with better eCrcl at 1 year post-transplant (b=0.21±0.1, p=0.04). In multiple regression analysis lower Δci (b=-0.2±0.09, p=0.05) and Δct (b=-0.29±0.1, p=0.02) were independently associated with a greater average MMF dose. There was no correlation between average MMF doses and incidence of acute rejection (p=0.68). ----- CONCLUSIONS: A higher average MMF dose over 1 year is associated with better renal function and slower progression of IF/TA, at least partly independent of its immunosuppressive effects