Immunosuppressive treatment for kidney transplantation

Razvoj novih imunosupresivnih lijekova i saznanja stečena primjenom različitih kombinacija ovih lijekova u imunosupresivnim protokolima dovela su do značajnog poboljšanja rezultata liječenja presađivanjem bubrega. Cilj imunosupresivnog liječenja smanjenje je neželjene imunosne aktivnosti, no ono često vodi u razvoj komplikacija kao što su infekcije, metabolički poremećaji, arterijska hipertenzija, tumori, te druge neželjene pojave. U ovom radu prikazani su mehanizmi djelovanja dostupnih imunosupresivnih lijekova, njihova primjena kod presađivanja bubrega i neželjena djelovanja. Imunosupresivni protokol koji se koristi u većine bolesnika obuhvaća inhibitor kalcineurina takrolimus ili ciklosporin, antimetabolit mikofenolat mofetil ili mikofenolnu kiselinu, i kortikosteroid. U ranom razdoblju nakon presađivanja za suzbijanje reakcije odbacivanja primjenjuje se jača imunosupresija pomoću većih doza imunosupresivnih lijekova ili dodavanjem indukcijskih agensa, monoklonskih ili poliklonskih antilimfocitnih protutijela. Uz navedene lijekove jednogodišnje preživljavanje bubrežnih presadaka iznosi više od 90 %, a učestalost akutnih reakcija odbacivanja do 15 %. U liječenju akutne reakcije odbacivanja posredovane stanicama primjenjuju se intravenski pulsne doze metilprednizolona, a rjeđe antilimfocitna protutijela. Za suzbijanje akutne humoralne reakcije odbacivanja, koju označava karakteristični patohistološki nalaz i dokaz donor-specifičnih protutijela u serumu primatelja, koriste se visoke doze intravenskih imunglobulina (IVIG) ili niske doze citomegalovirusnog hiperimunog globulina (CMVIG) u kombinaciji s plazmaferezom, do zadovoljavajućeg smanjenja titra antidonorskih protutijela. Rjeđe se primjenjuje imunoadsorpcija, rituksimab, alemtuzumab ili splenektomija. Ispitivanja imunosupresivnih tvari i njihovih mehanizama djelovanja dovela su do otkrića velikog broja potencijalnih lijekova, međutim, njihovoj primjeni u imunosupresivnom liječenju kod presađivanja bubrega moraju prethoditi velike randomizirane kontrolirane studije.The development of new immunosuppressive drugs and knowledge gained through their usage in different combinations in immunosuppressive protocols, has significantly improved results after renal transplantation. Immunosuppressive treatment aims at a reduction of unwanted immune activity, but complications often arise in the form of infections, metabolic disorders, arterial hypertension, tumors, and other side-effects. In this paper, we describe the mechanisms of action of available immunosuppressive drugs, their application for renal transplantation and their side-effects. In the majority of patients, the immunosuppressive protocol includes a calcineurin inhibitor, tacrolimus or cyclosporin, the antimetabolite mycophenolate mofetil or mycophenolic acid, and a corticosteroid. Early after transplantation, acute rejection is suppressed with higher doses of immunosuppressive drugs or an induction agent, monoclonal or polyclonal antilymphocytic antibodies. These drugs allow a one-year survival of renal allografts in over 90 % of cases, and an incidence of acute rejection reactions below 15 %. Acute cell-mediated rejection is treated with pulse doses of methylprednisolone intravenously, less often with antilymphocytic antibodies. Acute humoral rejection, characterized through specific pathohystologic changes and donor-specific antibodies in the recipient’s serum, is treated with high doses of intravenous immunoglobulines (IVIG) or low doses of cytomegalovirus hyperimmune globuline (CMVIG) together with plasmapheresis until a satisfactory reduction of anti-donor antibodies is obtained. Rarely, immunoadsorption, rituximab, alemtuzumab or splenectomy are applied. Investigations of immunosuppressive agents and their mechanisms of action have lead to the discovery of a large number of potential drugs. However, their application in the immunosupressive treament for renal transplantation has to be preceeded by large randomized controlled trials

Peritoneal dialysis

Peritonejska dijaliza (PD) postala je dobro afi rmirana metoda integriranog liječenja završnog stupnja bubrežnog zatajenja. Ona ima prednost kao prva metoda dijaliti čkog liječenja jer se u usporedbi s hemodijalizom dulje održava ostatna bubrežna funkcija, čime se značajno poboljšava kvaliteta života i preživljavanje bolesnika. PD je neophodna kod male djece i bolesnika sa srčanožilnim komplikacijama, kao što su dijabeti čari i starije osobe. U ovom radu prikazani su važni klinički aspekti , prednosti i komplikacije liječenja PD. Usavršavanje tehnologije i uvođenje biokompati bilnih otopina za PD, te individualizacija dijaliti čkog liječenja značajno smanjuju morbiditet i mortalitet bolesnika sa završnim stupnjem bubrežnog zatajenja.Peritoneal dialysis (PD) is a well-established method for the integrated care of end-stage renal disease. It is advantageous to start with PD as the fi rst dialyti c method, because it preserves residual renal functi on bett er than hemodialysis (HD) which leads to a signifi cant improvement in the quality of life and pati ent survival. PD is necessary for small children and pati ents with cardiovascular complicati ons, as are diabeti cs and the elderly. This paper addresses important clinical aspects, advantages and complicati ons of PD treatment. Improvement of technology, introducti on of biocompati ble soluti ons for PD, and individualisati on of dialyti c treatment signifi cantly reduce morbidity and mortality in pati ents with end-stage renal failure

Peritoneal dialysis

Peritonejska dijaliza (PD) postala je dobro afi rmirana metoda integriranog liječenja završnog stupnja bubrežnog zatajenja. Ona ima prednost kao prva metoda dijaliti čkog liječenja jer se u usporedbi s hemodijalizom dulje održava ostatna bubrežna funkcija, čime se značajno poboljšava kvaliteta života i preživljavanje bolesnika. PD je neophodna kod male djece i bolesnika sa srčanožilnim komplikacijama, kao što su dijabeti čari i starije osobe. U ovom radu prikazani su važni klinički aspekti , prednosti i komplikacije liječenja PD. Usavršavanje tehnologije i uvođenje biokompati bilnih otopina za PD, te individualizacija dijaliti čkog liječenja značajno smanjuju morbiditet i mortalitet bolesnika sa završnim stupnjem bubrežnog zatajenja.Peritoneal dialysis (PD) is a well-established method for the integrated care of end-stage renal disease. It is advantageous to start with PD as the fi rst dialyti c method, because it preserves residual renal functi on bett er than hemodialysis (HD) which leads to a signifi cant improvement in the quality of life and pati ent survival. PD is necessary for small children and pati ents with cardiovascular complicati ons, as are diabeti cs and the elderly. This paper addresses important clinical aspects, advantages and complicati ons of PD treatment. Improvement of technology, introducti on of biocompati ble soluti ons for PD, and individualisati on of dialyti c treatment signifi cantly reduce morbidity and mortality in pati ents with end-stage renal failure

Peritoneal dialysis

Peritonejska dijaliza (PD) postala je dobro afi rmirana metoda integriranog liječenja završnog stupnja bubrežnog zatajenja. Ona ima prednost kao prva metoda dijaliti čkog liječenja jer se u usporedbi s hemodijalizom dulje održava ostatna bubrežna funkcija, čime se značajno poboljšava kvaliteta života i preživljavanje bolesnika. PD je neophodna kod male djece i bolesnika sa srčanožilnim komplikacijama, kao što su dijabeti čari i starije osobe. U ovom radu prikazani su važni klinički aspekti , prednosti i komplikacije liječenja PD. Usavršavanje tehnologije i uvođenje biokompati bilnih otopina za PD, te individualizacija dijaliti čkog liječenja značajno smanjuju morbiditet i mortalitet bolesnika sa završnim stupnjem bubrežnog zatajenja.Peritoneal dialysis (PD) is a well-established method for the integrated care of end-stage renal disease. It is advantageous to start with PD as the fi rst dialyti c method, because it preserves residual renal functi on bett er than hemodialysis (HD) which leads to a signifi cant improvement in the quality of life and pati ent survival. PD is necessary for small children and pati ents with cardiovascular complicati ons, as are diabeti cs and the elderly. This paper addresses important clinical aspects, advantages and complicati ons of PD treatment. Improvement of technology, introducti on of biocompati ble soluti ons for PD, and individualisati on of dialyti c treatment signifi cantly reduce morbidity and mortality in pati ents with end-stage renal failure

Development of the Croatian model of organ donation and transplantation

Abstract During the past ten years, the efforts to improve and organize the national transplantation system in Croatia have resulted in a steadily growing donor rate, which reached its highest level in 2011, with 33.6 utilized donors per million population (p.m.p.). Nowadays, Croatia is one of the leading countries in the world according to deceased donation and transplantation rates. Between 2008 and 2011, the waiting list for kidney transplantation decreased by 37.2% (from 430 to 270 persons waiting for a transplant) and the median waiting time decreased from 46 to 24 months. The Croatian model has been internationally recognized as successful and there are plans for its implementation in other countries. We analyzed the key factors that contributed to the development of this successful model for organ donation and transplantation. These are primarily the appointment of hospital and national transplant coordinators, implementation of a new financial model with donor hospital reimbursement, public awareness campaign, international cooperation, adoption of new legislation, and implementation of a donor quality assurance program. The selection of key factors is based on the authors’ opinions; we are open for further discussion and propose systematic research into the issue

Inferior vena cava thrombosis due to polycystic kidney disease

Cilj: Adultna policistična bolest bubrega je najčešća nasljedna bolest bubrega.Tijekom godina dolazi do povećanja cisti, smanjenja funkcionalne nefronske mase i kompresije uvećanih bubrega na okolne strukture. U ovom radu prikazujemo pacijenticu s policističnom bolesti bubrega, kod koje se nakon presađivanja bubrega razvila tromboza donje šuplje vene. Prikaz pacijenta: Tri mjeseca nakon transplantacije kadaveričnoga bubrega u lijevu ilijačnu jamu 67-godišnja pacijentica hospitalizirana je zbog otoka desne noge. Kliničkim i ultrazvučnim pregledom ustanovljena je duboka venska tromboza desne noge i uvedena je terapija heparinom. S obzirom na to da nije dolazilo do poboljšanja, učinjen je pregled kompjutoriziranom tomografijom kojim je potvrđena duboka venska tromboza desne noge, ilijačnih vena desno i parcijalna tromboza distalnog dijela donje šuplje vene. Nalazi radiološke obrade ukazali su na pritisak desnog policističnog bubrega na donju šuplju venu te smo, zbog sprječavanja kompletnog venskog zastoja na razini donje šuplje vene, učinili nefrektomiju policističnog bubrega. Poslijeoperacijski tijek bio je uredan, otok noge se smanjio i funkcija bubrežnog presatka je ostala stabilna. Rasprava i zaključak: U pacijenata s velikim policističnim bubrezima kompresija donje šuplje vene može dovesti i do njezine tromboze. Indicirana je pravovremena nefrektomija.Aim: Autosomal dominant polycystic kidney disease is the most common renal hereditary disease. During many years renal cysts become larger, the functional nephron mass decreases and enlarged kidneys compress the surrounding structures. We present the case of a patient with polycystic kidney disease and inferior vena cava thrombosis after kidney transplantation. Case report: Three months after kidney transplantation into the left iliac fossa, the 67 year-old woman was admitted to our hospital due to swelling oft the right leg. Clinical and ultrasound examination revealed deep vein thrombosis of right leg and therapy with heparine was introduced. Since there was no improvement, a computerized tomography examination was performed that confirmed deep vein thrombosis of the right leg, thrombosis of iliac veins on the right side and partial thrombosis of the distal part of the inferior vena cava. As radiologic imaging revealed compression of the right polycystic kidney onto the inferior vena cava, we performed nephrectomy of the polycystic kidney to prevent complete thrombosis. The postoperative course was uneventful, with a regression of the right leg edema and stable graft function. Discussion and conclusion: In patients with large polycystic kidneys, compression of the inferior vena cava may lead to its thrombosis. A nephrectomy should be performed in time

STRUCTURED PREDIALYSIS EDUCATION PROGRAM – 10-YEAR EXPERIENCE AT RIJEKA UNIVERSITY HOSPITAL CENTRE

Uvod: Globalna procjena prevalencije kronične bubrežne bolesti (KBB) kreće se između 11-13 % uz 50 % starijih koji pokazuju znakove disfunkcije bubrega. Cilj istraživanja bio je utvrditi utječe li strukturirani predijalizni program na izbor liječenja, odabir metode i vrijeme početka nadomjesnog liječenja u svih bolesnika s posebnim osvrtom na starije bolesnike. Metode: Istraživanje je provedeno u Zavodu za nefrologiju, dijalizu i transplantaciju bubrega Klinike za internu medicinu KBC-a Rijeka. Retrospektivno smo analizirali 634 bolesnika s KBB, a koji su prijavljeni u nefrološku skrb u vremenu od 1. siječnja 2008. do kraja 2017. godine. Nadalje smo kao zasebnu skupinu izvojili bolesnike koji su u praćenom vremenu prvi puta prijavljeni nefrologu ili su započeli neku od nadomjesnih metoda u dobi od ≥65 godina. U skupini ≥65 godina analizirali smo podatke za 319 bolesnika. Bolesnike smo podijelili u tri skupine i pratili prema vremenskoj crti definiranoj u dob 1-3 izraženoj u godinama; od prvog nefrološkog pregleda do kraja 2017. Rezultati: Analizom nije pronađena statistički značajna razlika između skupina s obzirom na spol (p>0,670). Hi-kvadrat test pokazao je statistički značajnu vrijednost zastupljenosti šećerne bolesti tip 2 u odnosu na ostale uzroke bubrežne bolesti (p 0.670). The χ2-test showed statistical signifi cance for diabetes mellitus type 2 compared to other PKD causes (p<0.001). In group 1, 52.38% of 147 patients started some of the follow-up methods and 47.61% of patients were treated conservatively or were preparing for dialysis. The patients in this group statistically signifi cantly preferred PD compared to the other two groups (p<0.05). The ANOVA and LSD test in older adults showed a statistically signifi cant difference in the timeline in group 1 as compared to the other two groups (p<0.001). Gehan’s Wilcoxon test (p=0.00043) and Cox’s F-test (p=0.00001) in survival analysis showed a statistically signifi cant difference in survival between the groups (p<0.05). Survival analysis revealed that preparation or treatment after ten years of survival curve, there was no difference between the groups regardless of the choice. The study opened up the question of continuation with greater emphasis on planned, extended diagnosis after the fi rst patient referral, especially at an older age that might have interpreted survival more clearly

THE ROLE OF CORE DECOMPRESSION FOR THE TREATMENT OF FEMORAL HEAD AVASCULAR NECROSIS IN RENAL TRANSPLANT RECIPIENTS

Aseptična nekroza kosti je relativno rijetka komplikacija u primatelja bubrežnog transplantata. Ona može biti posljedica djelovanja brojnih uzročnih čimbenika, ali se najviše povezuje s liječenjem kortikosteroidima. Prikazat ćemo 62-godišnju bolesnicu s terminalnim bubrežnim zatajenjem, uzrokovanim poststreptokoknim glomerulonefritisom, koja se prije transplantacije bubrega 2,5 godine liječila peritonejskom dijalizom. Dvadeset mjeseci prije presađivanja bubrega, bolesnica je zbog akutnog poliradikuloneuritisa Guillaine Barré liječena visokim dozama kortikosteroida, uz primjenu imunoglobulina i plazmafereze. Kod transplantacije bubrega primijenjen je standardni imunosupresivni protokol, koji uključuje takrolimus, mikofenolat mofetil i kortikosteroid uz indukciju baziliksimabom. Četiri mjeseca nakon transplantacije, bolesnica počinje osjećati bolove u desnom kuku kod dužeg stajanja. Na radiogramu kuka ustanovljena su subhondralna prosvjetljenja u području lateralnog dijela cirkumferencije glavice, koja su se širila u proksimalni dio vrata desnog femura, dok pregled magnetskom rezonancom (MR) nije pokazao promjene u smislu aseptične nekroze kosti. Bolesnica je zbog progresije bolova i pozitivnog radiografskog nalaza, a unatoč negativnom nalazu MR-a, podvrgnuta kirurškom zahvatu dekompresije glavice bedrene kosti. Nakon zahvata bolovi su prestali i bolesnica se zadovoljavajuće oporavila. Kod primatelja bubrežnog transplantata treba rano posumnjati i utvrditi aseptičnu nekrozu kosti, jer pravodobno liječenje dekompresijom kosti može otkloniti bol te spriječiti ili odgoditi destrukciju kosti koja bi zahtijevala aloartroplastikuA vascular bone necrosis is a relatively rare but significant complication in renal transplant recipients because it causes progressive pain and invalidity. it can be the consequence of the action of numerous causative factors, but it is mostly connected to corticosteroid treatment.the underlying pathophysiologic mechanism is a diminished blood flow to the bone leading to necrosis and bone destruction. during the past 25-years period, 570 renal transplantations and five combined kidney and pancreas transplantations were performed in our centre. a part of the patients was lost to follow-up due to the separation of croatia from the former republic of Yugoslavia. After transplantation, we revealed aseptic necrosis of the femoral head in five female patients. all patients had a history of treatment with pulse doses of corticosteroids. at transplantation the average age of the patients was 52.2 yrs (range 46 to 62 yrs), and dialytic treatment before transplantation lasted in average 9.2 yrs (range 2.5 to 21.2 yrs). the period between renal transplantation and the development of clinical signs of avascular bone necrosis lasted in average 1.2 yrs (range 0.3 to 2.3 yrs). We will demonstrate our 62-year old female patient with terminal renal failure caused by post-streptococcal glomerulonephritis, who was treated with peritoneal dialysis 2.5 years before renal transplantation. twenty months before renal transplantation the patient received pulse doses of corticosteroids, together with immunoglobulins and plasmapheresis, for the treatment of an acute polyradiculoneuritis Guillaine barré. after transplantation a standard immunosuppressive protocol was applied which included tacrolimus, mycophenolate mofetil, corticosteroids and induction with basiliximab. four months after transplantation the patient started to feel pain in the right hip after longer standing, in addition to the earlier long-lasting problems caused by bilateral coxarthrosis. the pelvic radiograph showed subchondral radiolucencies in the lateral part of the head circumference spreading into the proximal part of the neck of the right femur, which indicated the presence of aseptic necrosis, but these changes could have also been caused by coxarthrosis. unexpectedly, magnetic resonance imaging (mri) did not reveal changes characteristic for avascular bone necrosis. due to the progressively worsening of pain and the radiographic finding, the patient was submitted to decompression surgery of the femoral head. the surgical procedure was performed under diascopic guidance (c-arm) which allowed the correct positioning of a kuerschner wire. a cannulated drill (diameter 4.0 mm) was placed over the wire and we performed two drillings of the spongiosis of the femoral head through to the subchondral area. Postoperatively, the patient was soon verticalized and advised to walk with crooks during a period of six weeks. this time is necessary to allow the mineralisation and strengthening of the bone which is now better vascularised. the patient recovered well and had no more pain. in renal transplant recipients it is most important to raise suspicion and verify the presence of avascular bone necrosis early, because timely bone decompression surgery can eliminate pain and cure the patient or it can prevent or delay bone destruction. When clinical signs of avascular bone necrosis arise and radiographic or standard mri findings are negative, additional investigations (i.e. sPect or mri with contrast) should be performed to confirm or exclude the diagnosis. in latter phases of the disease, surgical decompression of the femoral head cannot lead to permanent amelioration, and it is inevitable to perform more invasive surgical procedures like “resurfacing” or bone grafting in younger patients, or the implantation of total hip ndoprotheses