Monitoring and Treatment of Renal Transplant Patients During the COVID-19 Pandemic

Pandemija COVID-19 paralizirala je transplantacijske programe širom svijeta, uz visoke stope smrtnosti u populaciji bolesnika s transplantiranim bubregom. Suočeni s nepoznatim patogenom svjedočimo čitavom nizu manje ili više uspješnih pokušaja liječenja. Bolesnici s transplantiranim bubregom su posebno ugrožena skupina s obzirom na kronično stanje imunosupresije. Dodatan problem u liječenju COVID-19 predstavlja problem mogućih interakcija lijekova koji se rabe u liječenju SARS-CoV-2 s imunosupresivima, kao i rizik akutnih odbacivanja prilikom značajnih smanjivanja imunosupresije. Ponovno oživljavanje transplantacijskih programa zahtijevat će pažljivu procjenu rizika i dobrobiti za svakoga pojedinog bolesnika uz promišljanje načina uspostave međunarodne razmjene organa. Potrebna su daljnja istraživanja kako bi se odredio optimalan način liječenja SARS-CoV-2 u bolesnika s transplantiranim bubregom.The COVID-19 pandemic has paralyzed renal transplant programs worldwide, with high mortality rates in renal transplant patients. Faced with an unknown pathogen, we have witnessed numerous treatment attempts that have been more or less effective. Renal transplant recipients are at increased risk for morbidity and mortality from COVID-19 given their chronic immunocompromised state. Additional complications are potential interactions in drugs used for treatment of SARS-CoV-2 and immunosuppressive medications, as well as risk of acute allograft rejection associated with reduction of immunosuppression. The revival of renal transplant programs will require careful assessment of individual risk-to-benefit ratio for each patient, with step-by-step reintroduction of international organ exchange. Further studies are needed to determine optimal treatment of SARS-CoV-2 in renal transplant recipients

ISHOD TRANSPLANTACIJE BUBREGA KOD BOLESNIKA S LUPUSNIM NEFRITISOM – ISKUSTVO JEDNOG CENTRA I PREGLED LITERATURE

Aims: Kidney transplantation (KT) is the treatment of choice for end-stage kidney disease in patients with systemic lupus erythematosus (SLE). Still, these patients tend to fare worse than other patient groups with chronic kidney failure. The main aim of this retrospective observational study was to evaluate the outcomes of KT in patients with SLE. Methods: Data were obtained from medical records and charts. Results: From February 2007, a total of 12 SLE patients, average age 37 (18-56) years, underwent deceased donor KT at our Center. Comorbidities were primarily cardiovascular. At the time of KT, 91.7% of patients showed no signs of SLE activity. Immunological matching was favorable and all allografts showed satisfactory initial function. Median graft survival for the whole patient population was 41 (0-93) months. In 66.7% of patients with stable graft function, median survival was 61 (22-93) months, in three patients longer than fi ve years. One patient died 4 months after the transplantation from neurologic complications, whereas 25% of allografts were lost in the early post-transplant period, in 0-5 months after KT. Our patient outcomes showed no clear correlation between age, previous KT or number of comorbidities. Episodes of acute rejection or recurrent lupus nephritis brought a higher risk of poor outcome. Conclusion: While there still are many unanswered questions relating to the management of this immunologically very sensitive group of patients, forming a multidisciplinary transplantation team would enable pre-transplant evaluation of SLE patients with possible risk assessment and adjustment of follow up strategy to achieve an optimal survival outcome.Uvod i ciljevi: Transplantacija bubrega metoda je izbora u liječenju završnog stadija kronične bubrežne bolesti u bolesnika s lupusnim glomerulonefritisom (LN). Ipak, u usporedbi s drugim bolesnicima ova skupina unatoč napretku u liječenju i dalje pokazuje lošiji ishod. Glavni cilj ovog istraživanja bio je usporediti ishode našeg Centra s ishodima drugih studija te raspraviti nove mogućnosti u praćenju i liječenju ove skupine pacijenata. Ispitanici i metode: Svi istraživani parametri prikupljeni su iz dostupne medicinske dokumentacije. Rezultati: 12 bolesnika sa SLE, prosječne dobi 37 (18-56) godina, učinjena je transplantacija u našem Centru od veljače 2007. godine. Svi su bolesnici bili primatelji presatka kadaveričnog darivatelja. Najčešći komorbiditeti bile su kardiovaskularne bolesti. U vrijeme transplantacije 91,7% bolesnika bilo je u potpunoj serološkoj i kliničkoj remisiji osnovne bolesti. Stupanj tkivne podudarnosti bio je zadovoljavajući, a uspostavljanje bubrežne funkcije promptno u svih ispitanika. Prosječno vrijeme preživljenja presatka iznosilo je 41 (0-93) mjesec. Kod 66,7% bolesnika sa stabilnom bubrežnom funkcijom, to je vrijeme iznosilo 61 (22-93) mjesec, za tri je presatka zabilježeno preživljenje dulje od 5 godina. Tri su bolesnika graftektomirana (25%), dok je u jedne olesnice zabilježen smrtni ishod. Gubitak presadaka nastupio je u ranom posttransplantacijskom razdoblju – od 0 do 5 mjeseci nakon transplantacije. Zaključak: Iako postoje brojna neistražena i neodgovorena pitanja vezana uz zbrinjavanje ove imunološki vrlo osjetljive i zahtjevne skupine bolesnika, pažljiva skrb prije i nakon transplantacije te uska suradnja nefrologa i imunologa omogućavaju dobar ishod uz značajno povećanje kvalitete života

KIDNEY TRANSPLANTATION IN PATIENTS WITH FOCAL SEGMENTAL GLOMERULOSCLEROSIS

Uvod i ciljevi: Povratak fokalne segmentalne glomerularne skleroze (FSGS) u presadak i dalje ostaje važna prepreka u postizanju dugoročno zadovoljavajućih rezultata transplantacije bubrega. Glavni cilj istraživanja bio je procijeniti ishode bolesnika praćenih u našem Centru te raspraviti nove mogućnosti u liječenju ove skupine bolesnika. Ispitanici i etode: U istraživanje su uključeni svi bolesnici (n=30; 33,3% muškaraca) s dijagnozom FSGS vlastitih bubrega, liječeni transplantacijom u razdoblju od listopada 2007. i listopada 2013. Svi istraživani parametri prikupljeni su iz dostupne medicinske dokumentacije. Rezultati: 29 bolesnika imalo je nekolabirajuću FSGS (ncFSGS), dok je u jednog bolesnika ustanovljena kolabirajuća varijanta bolesti (cFSGS). Kadaverični presadak primilo je 96,7 % bolesnika. Ukupno preživljenje bolesnika tijekom praćenja iznosilo je 90 %. Osamdeset posto bolesnika imalo je zadovoljavajuću funkciju presatka uz medijan preživljenja 49,15 (0,5-84) mjeseci. Incidencija povratka bolesti u presadak bila je 20 % (6/30), a 3 presatka su promptno izgubila svoju funkciju zbog cFSGS. Skupina bolesnika sa cFSGS varijantom izražavala je višu proteinuriju značajno ranije u posttransplantacijskom razdoblju (P <0,05), što se u konačnici odrazilo težom kliničkom slikom i ranim gubitkom presatka (3-6 mjeseci nakon transplantacije). Terapijskim izmjenama plazme uspješno su liječena dva bolesnika s ncFSGS, dok dva bolesnika s cFSGS varijantom nisu odgovorila na terapiju (50 %-tni odgovor na terapiju). Zaključak: Iako je rizik za povratak FSGS u presadak visok, transplantacija bubrega i dalje je zlatni standard u liječenju bolesnika s FSGS. Neophodno je bez odgađanja učiniti biopsiju presatka u svih bolesnika s razvojem proteinurije kako bi se na vrijeme započela specifi čna terapija i poboljšao ishod.Aims: Posttransplant recurrence of FSGS remains an obstacle towards satisfactory long-term kidney allograft survival. We aimed to evaluate the outcomes of kidney transplantation (KTx) in patients with FSGS treated at our Center and discuss available management options for improved outcomes in this group of patients. Patients and Methods: All patients (n=30; 33.3% male) with histological evidence of FSGS on a native kidney biopsy transplanted during the period between October 2007 and October 2013 were analyzed. Data were obtained from the medical records and charts. Results: 29 patients had a non-collapsing FSGS (ncFSGS), while one had collapsing FSGS (cFSGS). 96.7% of patients received deceased donor kidney allograft. Overall patient survival was 90% during the follow-up period. 80% of patients had satisfactory allograft function, with median allograft survival of 49.15 (range, 0.5-84) months. The incidence of recurrence was 20% (6/30), with 3 allografts lost rapidly due to cFSGS. cFSGS group had higher urine protein excretion earlier in the posttransplant period (P < 0.05), which resulted with more severe clinical presentation and early allograft loss (3-6 months posttransplant). Therapeutic plasma exchange (TPE) was successfully employed in 2 patients with ncFSGS, while 2 patients in the cFSGS group did not respond to treatment (response rate 50%). Conclusion: Although an increased risk of recurrence exists, KTx remains the treatment of choice for patients with FSGS. Immediate allograft biopsy should be performed in all patients developing proteinuria and prompt therapy should be started in order to achieve better outcomes

AGREGACIJA TROMBOCITA U ZAVRŠNOM STADIJU ZATAJIVANJA BUBREGA – RAZLIKE IZMEĐU BOLESNIKA KOJI SU LIJEČENI HEMODIJALIZOM I PERITONEJSKOM DIJALIZOM

End-stage renal disease patients (ESRD) suffer from procoagulant abnormalities that lead to excessive cardiovascular events, as well as from platelet dysfunction manifesting as an increased risk of bleeding. The exact pathogenesis of complex hemostatic disorders in ESRD patients is not completely understood. The aim of our study was to investigate the possible different effects of hemodialysis (HD) and peritoneal dialysis (PD) on platelet function in patients with ESRD by using the platelet function analyzer (PFA-100) which in vitro simulates the process of aggregation and platelet activation. Tests were performed with collagen/epinephrine (COL/EPI) and collagen/adenosine-5-diphosphate (COL/ADP) cartridges. The study included 44 patients with ESRD undergoing regular HD (n=32) or PD (n=12). Although there were no significant differences in COL/EPI and COL/ADP tests, it is indicative that more than 50% of HD patients had COL/EPI test values above the upper limit. These findings correlated with a higher chance for bleeding in HD group.Additionally, patients in HD group were significantly older and had significantly lower platelet count compared to PD patients.Završni stadij kronične bubrežne bolesti obilježen je različitim prokoagulantnim odstupanjima koja dovode do razvoja tromboembolijskih komplikacija uz istodobno poremećenu funkciju trombocita s posljedičnim porastom rizika za nastanak krvarenja. Točna etiologija složenih hemostatskih poremećaja u završnom stadiju kronične bubrežne bolesti nije u potpunosti razjašnjena. Cilj ovoga istraživanja bio je usporediti učinak hemodijalize i peritonejske dijalize na funkciju tromobocita kod bolesnika u završnom stadiju kronične bubrežne bolesti primjenom analizatora funkcije trombocita (PFA-100) koji in vitro stimulira proces aktivacije i agregacije trombocita. Ispitivanje je provedeno na 2 testa (COL/EPI i COL/ADP) koji mjere vrijeme potrebno cirkulirajućoj krvi da okludira membranu obloženu kolagenom i adrenalinom (COL/EPI) odnosno kolagenom i ADP-om (COL/ADP). U istraživanje su bili uključeni bolesnici na hemodijalizi (n=32) odnosno peritonejskoj dijalizi (n=12). Premda nije zabilježena statistički značajna razlika između testova COL/EPI i COL/ADP, indikativno je da su u više od 50% ispitanika na hemodijalizi vrijednosti testa COL/EPI bile iznad gornje granice referentnog intervala. Ovi rezultati mogu se povezati s većom mogućnosti krvarenja u bolesnika na hemodijalizi. Uz to, bolesnici na hemodijalizi bili su značajno stariji te su imali statistički značajno niži broj trombocita u odnosu na ispitanike na peritonejskoj dijalizi

Metabolička acidoza - zanemarujemo li je nakon transplatacije bubrega?

Despite prolonged survival and better quality of life as compared to dialysis, kidney transplantation frequently presents with a complex set of medical issues that require intensive management to protect graft function. Metabolic acidosis has an impact on several metabolic complications such as mineral and muscle metabolism, nutritional status and anemia. It may also have an effect on graft function, possibly through the stimulation of adaptive mechanisms aimed at maintaining acid-base homeostasis. We investigated current practice in the evaluation of metabolic acidosis at one of the largest transplant centers in the Eurotransplant region. Adult renal transplant recipients having received allograft from January 2011 to August 2012 were included in the investigation. We recorded the frequency of measuring the parameters of venous blood gas analysis, as well as creatinine and urea levels, creatinine clearance, proteinuria, calcium, phosphate and potassium blood levels, body mass index and the time spent on dialysis prior to kidney transplantation. Out of 203 patients who had received renal allograft at our institution during the observed period, 191 (124 males and 67 females, age range from 18 to 77 years) were enrolled in the study. Of these, only 92 (48.167%) patients had parameters of venous blood gas analysis measured at some time after kidney transplantation. Acid-base status was determined more often in males (77 males vs. 22 females, p=0.001). Patients with pH/blood gas analysis performed were found to have significantly higher creatinine and urea levels and significantly lower creatinine clearance (p<0.001 both). Serum calcium levels were also significantly lower in this group of patients (p<0.001). Metabolic acidosis is a very important clinical issue that needs to be monitored in every transplant recipient. Its effects on graft function, nutritional status, anemia and bone mass are complex but can be successfully managed. Our study showed metabolic acidosis to be linked with significantly higher creatinine and urea levels, decreased creatinine clearance and lower calcium levels. Nevertheless, metabolic acidosis still stays a highly underestimated problem among nephrologists dealing with transplant recipients. We suggest regular determination of the acid-base status in renal transplant recipients.Metabolička acidoza je česta komplikacija vezana uz progresivan gubitak bubrežne funkcije. Njezin utjecaj na status uhranjenosti, razvoj anemije, koštanu masu i funkciju presađenog bubrega je vrlo složen, ali se može učinkovito spriječiti. Istražili smo koliko se određivanju i praćenju acidobaznog statusa (ABS) posvećuje pozornosti u jednom od najvećih transplantacijskih centara unutar organizacije Eurotransplant. U istraživanje su uključeni svi odrasli primatelji bubrega u razdoblju od siječnja 2011. do kolovoza 2012. godine. Tijekom promatranog razdoblja transplantirano je 203 bolesnika, a 191 bolesnik uključen je u istraživanje (124 muškarca i 67 žena, raspona dobi od 18 do 77 godina). Statistička analiza pokazala je da je u poslijetransplantacijskom razdoblju ABS bio određen samo u 92 (48,167%) bolesnika. ABS je češće određivan muškarcima (p=0,001). Bolesnici s određivanim ABS imali su značajno više vrijednosti kreatinina i ureje (p<0,001), kao i značajno niži klirens kreatinina (p<0,001). Ova skupina bolesnika imala je i značajno niže serumske koncentracije kalcija (p<0,001). Metabolička acidoza je važno kliničko pitanje koje je potrebno pažljivo razmotriti kod svakog primatelja bubrega. Naše istraživanje pokazalo je da je metabolička acidoza povezana sa značajno višim vrijednostima kreatinina i ureje, smanjenim klirensom kreatinina i nižim vrijednostima kalcija. Unatoč tome, metabolička acidoza ostaje uvelike zanemaren problem kod ove skupine bolesnika. Preporučamo redovito praćenje acidobaznog statusa svih bolesnika s presađenim bubregom

Transplantacija bubrega od preminulih darivatelja s povišenom zadnjom vrijednosti kreatinina

The increasing number of possible recipients for kidney transplantation and relatively unchanged number of organ donors has led to consideration of alternative strategies and expansion of deceased donor criteria in order to expand donor pool. Previously, kidneys from expanded criteria donors (ECD) were strongly underestimated because of the conventional opinion suggesting these kidneys to have a higher rate of preservation injury, delayed graft function, rejection and nonfunction. Reducing the difference between graft outcome in patients transplanted from ECD and standard criteria donor (SCD) is one of the goals of many respectable kidney transplantation centers. This assignment includes major concern about reduction of cold ischemia time, recipient selection, novel and adapted immunosuppressive regimens, increased nephron mass by dual kidney transplantation, and using histologic criteria for marginal donor graft selection. There are not many reports on the outcome of kidneys transplanted from donors with acute renal failure and high terminal creatinine. This review presents the exact definition of marginal donor, especially donor with acute renal failure. The management of such grafts during preimplantation and implantation period, outcomes and post-transplantation care are the main assignments for transplantation teams. Recipients of such grafts should be well informed about the possibilities and potential complications and sign their informed consent thereafter. Some respectable studies have shown that under certain, highly controlled conditions, these kidneys can be used safely, with excellent short- and long-term outcomes.Ukupni broj darivatelja organa u posljednje je vrijeme nepromijenjen, a sve veći broj potencijalnih primatelja bubrega na listi čekanja doveo je do razvoja novih strategija i proširenja kriterija kojima se procjenjuje mogući darivatelj organa. Prije se smatralo da su bubrezi darivatelja po proširenim kriterijima lošiji zbog veće učestalosti oštećenja tijekom konzerviranja bubrega, češće odgođene funkcije presatka, odbacivanja i primarne afunkcije organa. Danas je mnogim velikim transplantacijskim centrima cilj smanjenje razlike u ishodu presatka transplantiranog s darivatelja po proširenim kriterijima i darivatelja po standardnim kriterijima. Ovaj cilj uključuje strogu kontrolu u skraćivanju vremena hladne ishemije, odabira primatelja, prilagođene protokole imunosupresije, povećanje mase nefrona s transplantacijom “dva u jedan” i primjenu histoloških kriterija u odabiru grafta marginalnog darivatelja. Zasad nema mnogo objavljenih radova o ishodu transplantiranog bubrega darivatelja s akutnim zatajenjem bubrega ili visokom zadnjom vrijednosti kreatinina u serumu. Namjera ovoga preglednog članka je prikazati najnoviju definiciju marginalnog darivatelja i darivatelja s akutnim zatajenjem bubrega. Primatelji bubrega darivatelja po proširenim kriterijima moraju tijekom prijetransplantacijske obrade biti dobro obaviješteni o svim mogućnostima i komplikacijama takvog postupka, te potpisati obaviješteni pristanak. Poznate studije pokazale su da se pod strogo kontroliranim kriterijima bubrezi darivatelja po proširenim kriterijima mogu sigurno transplantirati odabranim primateljima, s dobrim kratkoročnim i dugoročnim ishodom

Reaktiviranje virusa Herpes Zostera u bolesnika liječenih hemodijalizom: očitovanje, liječenje, komplikacije i ishod

Varicella zoster virus reactivation often occurs in the setting of impaired immunity, which is generally present in patients with end-stage renal disease (ES RD). Therapy for varicella zoster virus infection is well established. However, it is often been forgotten that acyclovir dosage should be adjusted to renal function. We point to the problem encountered in clinical practice when ES RD patient presents with cutaneous herpes zoster and neurological symptoms. Clinical findings alone may prove inadequate to determine whether neurological deficit is caused by infection of the central nervous system or is a consequence of acyclovir induced neurotoxicity.Do reaktiviranja varicella zoster virusa dolazi u bolesnika s narušenim imunim sustavom, što je gotovo univerzalna pojava u bolesnika sa završnim stadijem kronične bubrežne bolesti. Iako je liječenje infekcije varicella zoster virusom dobro poznato, često se zaboravlja da je potrebna prilagodba doze aciklovira s obzirom na bubrežnu funkciju. Želimo naglasiti problem pojave kožnog oblika herpes zostera u kombinaciji s neurološkim simptomima. Na osnovi kliničkog nalaza ponekad nije moguće jasno razabrati radi li se o infekciji središnjega živčanog sustava ili o neurotoksičnosti aciklovira

ACID-BASE STATUS IN PATIENTS TREATED WITH PERITONEAL DIALYSIS

Peritonejska dijaliza je jednostavna metoda nadomještanja bubrežne funkcije koja je i financijski isplativija u usporedbi s hemodijalizom. Brojna istraživanja pokazala su njenu učinkovitost u održavanju ostatne bubrežne funkcije, odgađanju nastupa uremijskih komplikacija i očuvanju acidobazne ravnoteže, ali i bolji posttransplantacijski ishod u bolesnika liječenih tom metodom. Unatoč tome peritonejska dijaliza se još uvijek nije izborila za mjesto koje zaslužuje u liječenju završnog stadija kronične bubrežne bolesti. Metabolička acidoza je česta komplikacija vezana uz progresivan gubitak bubrežne funkcije. Njezin utjecaj na koštanu i mišićnu masu, razvitak anemije, ostatnu bubrežnu funkciju kao i funkciju presađenog bubrega je vrlo složen, ali se može učinkovito spriječiti. Glavni cilj našeg istraživanja bio je utvrditi učinkovitost peritonejske dijalize u održavanju acidobazne ravnoteže. U istraživanje je uključeno 28 bolesnika liječenih metodom peritonejske dijalize. Prosječno vrijeme liječenja iznosilo je 32,39±43,43 mjeseci. Kod svih su bolesnika korištene otopine puferirane isključivo dodatkom laktata. U potpunosti uredan acidobazni status imalo je 73,07 % bolesnika, a 11,54 % bilo je u stanju blage metaboličke acidoze. Blaga metabolička alkaloza zabilježena je kod identičnog udjela bolesnika. U jednog je bolesnika utvrđeno postojanje mješovitog poremećaja, alkaloze s respiratornom i metaboličkom komponentom. Ovim smo radom pokazali da se acidobazna ravnoteža u bolesnika liječenih metodom peritonejske dijalize zaista može vrlo uspješno održavati čak i primjenom isključivo laktatom puferiranih otopina koje su nizom istraživanja proglašavane inferiornijima u odnosu na bikarbonatne. Uz dobru edukaciju i pažljivu primjenu metode, te temeljitu i čestu evaluaciju ovoj se skupini itekako omogućuje kvalitetno kontinuirano nadomještanje bubrežne funkcije uz dobru kvalitetu života.When compared to hemodialysis, peritoneal dialysis is very simple yet low cost method of renal replacement therapy. Series of studies have shown its superiority in preserving residual renal function, postponing uremic complications, maintaining the acid-base balance and achieving better post-transplant outcome in patients treated with this method. Despite obvious advantages, its role in the treatment of chronic kidney disease is still not as important as it should be. Metabolic acidosis is an inevitable complication associated with progressive loss of kidney function. Its impact on mineral and muscle metabolism, residual renal function, allograft function and anemia is very complex but can be successfully managed. The aim of our study was to evaluate the efficiency in preserving the acid-base balance in patients undergoing peritoneal dialysis at Zagreb University Hospital Center. Twenty-eight patients were enrolled in the study. The mean time spent on the treatment was 32.39±43.43 months. Only lactate-buffered peritoneal dialysis fluids were used in the treatment. Acid-base balance was completely maintained in 73.07% of patients; 11.54% of patients were found in the state of mild metabolic acidosis, and the same percentage of patients were in the state of mild metabolic alkalosis. In one patient, mixed alkalosis with respiratory and metabolic component was present. The results of this study showed that acid-base balance could be maintained successfully in patients undergoing peritoneal dialysis, even only with lactate-buffered solutions included in the treatment, although they were continuously proclaimed as inferior in comparison with bicarbonate-buffered ones. In well educated and informed patients who carefully use this method, accompanied by the attentive and thorough care of their physicians, this method can provide quality continuous replacement of lost renal function as well as better quality of life

Expression of BMP-2 in vascular endothelial cells of recipient may predict delayed graft function after renal transplantation

BACKGROUND/AIMS: Delayed graft function (DGF) is associated with adverse outcomes after renal transplantation. Bone morphogenetic protein-2 (BMP-2) is involved in both endothelial function and immunological events. We compared expression of BMP-2 in epigastric artery of renal transplant recipients with immediate graft function (IGF) and DGF. ----- METHODS: 79 patients were included in this prospective study. Patients were divided in IGF group (64 patients) and DGF group (15 patients). BMP-2 expression in intima media (BMP2m) and endothelium (BMP2e) of epigastric artery was assessed by immunohistochemistry. ----- RESULTS: Lower intensity of BMP2e staining was recorded in DGF compared to IGF. In DGF patients, 93% had no expression of BMP2e and 7% had 1st grade expression, compared to 45% and 41% in IGF group, respectively (P=0.001) (P<0.001 for no expression and P = 0.015 for 1st grade expression). Patients who had BMP2e staining positive had lower odds for DGF (OR 0.059 [0.007, 0.477]) and this remained significant even after adjustment for donor and recipient variables, cold ischemia time, and immunological matching (OR 0.038 [0.003, 0.492]). ----- CONCLUSIONS: Our results demonstrate that BMP-2 expression in endothelial cells of epigastric arteries may predict development of DGF