Amanda Robertson

Successful ABO-incompatible kidney transplantation with antibody removal and standard immunosuppression.

ABO‐incompatible (ABOi) kidney transplantation is an established therapy, though its implementation to date has been in part limited by the requirement for additional immunosuppression. Here, we describe the outcomes of 37 patients undergoing ABOi kidney transplantation utilizing perioperative antibody depletion and receiving an identical tacrolimus‐based immunosuppressive regimen to contemporaneous ABO‐compatible (ABOc) recipients, with the exception that mycophenolate was commenced earlier (7–14 days pretransplant). Antibody depletion was scheduled according to baseline anti‐ABO antibody titer (tube IAT method: median 1:128, range 1:8 to 1:4096). Patient and graft survival for the 37 ABOi recipients was 100% after a median 26 months (interquartile range [IQR] 18–32). Eight rejection episodes (two antibody‐mediated and six cellular) in ABOi recipients were successfully treated with biopsy‐proven resolution. Latest median eGFR is 50 mL/min × 1.73 m2 (IQR 40–64) for ABOi patients and 54 mL/min × 1.73 m2 (IQR 44–66) in the ABOc patients (p = 0.25). We conclude that ABOi transplantation can be performed successfully with perioperative antibody removal and conventional immunosuppression. This suggests that access to ABOi transplantation can include a broader range of end‐stage kidney disease patients.

IS TEMPORAL ARTERY BIOPSY A WORTHWHILE PROCEDURE

Background:  Temporal artery biopsy (TAB) has been accepted as the gold standard for the diagnosis of giant cell arteritis (GCA) or temporal arteritis (TA) even though it is of low sensitivity and specificity. Current medical practice recommends commencing high dose steroids before performing a biopsy, and the continued use of long‐term steroids even if biopsy is negative but clinical suspicion of the diagnosis is high. The aim of the present study is to determine if TAB results actually changes the management of patients suspected of GCA or TA.

ABO‐Incompatible Renal Transplantation Without Antibody Removal Using Conventional Immunosuppression Alone

ABO incompatible living donor renal transplantation (ABOi) can achieve outcomes comparable to ABO compatible transplantation (ABOc). However, with the exception of blood group A2 kidneys transplanted into recipients with low titer anti‐A antibody, regimens generally include antibody removal, intensified immunosuppression and splenectomy or rituximab. We now report a series of 20 successful renal transplants across a range of blood group incompatibilities using conventional immunosuppression alone in recipients with low baseline anti‐blood group antibody (ABGAb) titers. Incompatibilities were A1 to O (3), A1 to B (2), A2 to O (2), AB to A (2), AB to B (1), B to A1 (9), B to O (1); titers 1:1 to 1:16 by Ortho. At 36 months, patient and graft survival are 100%. Antibody‐mediated rejection (AbMR) occurred in one patient with thrombophilia and low level donor‐specific anti‐HLA antibody. Four patients experienced cellular rejection (two subclinical), which responded to oral prednisolone. This series demonstrates that selected patients with low titer ABGAb can undergo ABOi with standard immunosuppression alone, suggesting baseline titer as a reliable predictor of AbMR. This reduces morbidity and cost of ABOi for patients with low titer ABGAb and increases the possibility of ABOi from deceased donors.

Two-stage brachiobasilic arteriovenous fistula for chronic haemodialysis access

Background:  Many haemodialysis patients are unable to have or maintain distal upper limb arteriovenous (AV) fistulas because of inadequate veins or arteries and therefore require more proximal access. We have reviewed our experience with a two‐stage brachiobasilic AV haemodialysis fistula fashioned in the arm.

CAROLI’S SYNDROME AND ADULT POLYCYSTIC KIDNEY DISEASE

Caroli’s disease is a cystic disease of the liver, which has been rarely associated with adult onset polycystic kidney disease. Three cases have been reported in the English Medline search. The presentation of this fourth case discusses the issues surrounding the treatment of Caroli’s disease in the setting of a renal transplant.

Management of blunt and penetrating biliary tract trauma.

BACKGROUND Penetrating or blunt injury to the biliary tree remains a rare complication of trauma occurring in 0.1% of trauma admissions. Because of the different presentations, sites of biliary tract injury, and associated organ injury, there are many possible management pathways to be considered. METHODS A retrospective analysis of prospectively gathered data was performed for all gallbladder and biliary tract injuries presenting to the trauma service or hepatobiliary unit of the Royal Melbourne Hospital between January 1, 1999, and March 30, 2011. RESULTS There were 33 biliary injuries in 30 patients (0.1%) among 26,014 trauma admissions. Three of the 30 patients (10%) died. Of 10 gallbladder injuries, 8 were managed with cholecystectomy. There were 23 injuries to the biliary tree. Fourteen patients had injuries to the intrahepatic biliary tree of which seven involved segmental ducts. Of these, four segmental duct injuries required hepatic resection or debridement. Nine patients had injury to the extrahepatic biliary tree of which five required T-tube placement ± bilioenteric anastomosis and one a pancreaticoduodenectomy. CONCLUSION Biliary injury is a rare but important consequence of abdominal trauma, and good outcomes are possible when a major trauma center and hepatopancreaticobiliary service coexist. Cholecystectomy remains the gold standard for gallbladder injury. Drainage with or without endoscopic stenting will resolve the majority of intrahepatic and partial biliary injuries. Hepaticojejunostomy remains the gold standard for complete extrahepatic biliary disruption. Hepatic and pancreatic resection are only required in the circumstances of unreconstructable biliary injury. LEVEL OF EVIDENCE Therapeutic study, level V.

Stent-related ureteric obstruction in paediatric renal transplantation.

The rates of ureteric obstruction and complications for use of externally draining uretero-vesico-cutaneous (external) stents (Group 1: n=39) and the use of internal uretero-vesical (double-J) stents (Group 2: n=16), in 55 of 64 consecutive paediatric renal-transplant recipients, performed at our institution between January 1996 and December 2003, have been compared. Serum creatinine levels pre and post-operatively and pre and post-stent removal were recorded. The diagnosis of ureteric obstruction was based on an increase in serum creatinine of ≥20%, in conjunction with ultrasound evidence of hydronephrosis or hydroureter, where other causes of renal dysfunction were excluded. Ureteric obstruction occurred in 13 of the 39 patients (33.3%) in Group 1, compared with only one case of ureteric obstruction in the 16 patients (6.25%) in Group 2 (OR=7.5, 95% CI=0.8–70, P=0.038). There was no evidence of a difference in the number of urinary tract infections (9/39 in Group 1, 6/16 in Group 2, OR=0.5, 95% CI=0.14 to 1.8, P=0.275) or the mean length of hospital stay (10.9 days in Group 1, 10.1 days in Group 2, 95% CI=−2.3 to 4 days, P=0.565) between the two groups. Glomerular filtration rate (GFR) improved in the week after stent removal in Group 2, but deteriorated in Group 1 (P=0.07). This non-randomised comparison of stent types supports the use of prophylactic double-J stents in paediatric renal transplantation- in terms of decreased ureteric complications and improved renal function post-stent removal.

Renal allograft re-use and herpetic re-infection

A middle‐aged man received a kidney transplant from a deceased multi‐organ donor. The recipient suffered cardiac arrest several days post‐operatively and sustained hypoxic brain injury and was declared brain dead. Following the familys consent, the allograft kidney was retrieved and re‐transplanted into a man with end‐stage renal failure secondary to reflux nephropathy. The liver was not transplanted due to suspicion of fatty changes based on macroscopic appearance. After transplantation of other organs, liver histology revealed coagulative parenchymal necrosis with nuclear inclusions and moderate parenchymal cholestasis, suggestive of herpes viral hepatitis. Renal implantation biopsy showed histiocytes with enlarged nuclei containing viral inclusions in the capsular fibrous tissue, with positive immunostaining for herpes simplex virus (HSV). Anti‐viral therapy was commenced immediately after obtaining histological evidence of donor HSV infection. Our recipient had pre‐formed immunoglobulin G antibodies to HSV‐1 and HSV‐2, and was immunoglobulin M negative pre‐transplant. HSV viraemia was detected day 5 post‐transplant with a viral load of 7688 copies/mL by polymerase chain reaction assay. The recipient completed a 30 day course of intravenous ganciclovir before switching to oral valganciclovir as standard cytomegalovirus prophylaxis. The HSV polymerase chain reaction became undetectable on day 7 of intravenous ganciclovir and has remained undetectable. The patient remains well 9 months post‐transplant with an estimated glomerular filtration rate of 61 mL/min per 1.73 m2. Although renal allograft re‐use has been shown to be technically possible with a good outcome in this recipient, this does raise issues including assessment of allografts that have undergone repeated severe ischaemic insults and the potential of transmission of infections.

Living donor transplantation: is there inequality of access?

In the management of end-stage kidney disease (ESKD), the relative benefits of kidney transplantation compared to dialysis in terms of patient survival and quality of life are unequivocal. The evidence base so overwhelmingly favours transplantation that the establishment of a new Federal Government Authority (Australian Organ and Tissue Donation and Transplantation Authority (AOTDTA)) at the beginning of 2009 aimed at increasing the number or transplants for patients reaching ESKD or stage 5 chronic kidney disease comes as no surprise. The AOTDTA has also established an embryonic national scheme for live paired kidney donation or so-called ‘paired kidney exchange’ but surprisingly has no mandate or resource to look at increasing the numbers of traditional live kidney donations. Living kidney donation also needs to remain successful if we are to provide better patient outcomes, and as such, access to transplantation should be equitable for all potential kidney transplant recipients across Australia. In Victoria and Tasmania, this is certainly one of the aspirations of the Victorian Department of Health Renal Health Care Network (RHCN). Professional approaches and clinical pathways leading towards live donation, however, appear to be quite different between individual transplantation units. Data (unadjusted for case-mix and/or co-morbidities) extracted from the publically available ANZDATA Annual Reports and collected for the 6 inclusive years between 2003 and 2008 inclusive for the five main Victorian Transplanting Centres and the associated referring Victorian and Tasmania Dialysis Centres demonstrate strikingly different transplantation rates compared to the numbers of patients remaining on dialysis. Transplantation rates (Table 1), measured as the mean ratio % (number of transplants/calendar year: number of patients on dialysis at the end of the year (with 95% confidence intervals (CI))) and compared (Pearson chi for observed versus expected) to the same ratio over the same six periods for the remainder of Australia are significantly different for all transplants (P = 0.013) and living donor transplants (P = 0.02) but not deceased donor transplants (P = 0.301). For living donor transplants, the Australian mean (95% CI) was 3.0% (2.7–3.3%). The five Victorian units showed a large variation in this ratio ranging between 1.2% (0.9–1.5%) (Unit 5) and 5.0% (3.0–7.0%) (Unit 3). Unit 5 has a living donor transplantation rate ~ 50% of the national benchmark (Table 1). Favourable attitudes to living donor transplantation do not always translate into practice. In Australia, the relatively recent survey responses of 184 practicing nephrologists and trainees suggested high levels of support of live kidney donation with 95% of respondents indicating that they would recommend it to a suitable donor. Interestingly, however, only 43% would continue to recommend live kidney donation to a potential donor, where their relative’s ESKD had been attributed to diabetes. Although diabetes is an increasingly important cause of ESKD, with some prospect therefore of limiting the use of live donors, the distribution of diabetic disease across centres would not seem at all likely to explain the marked differences currently observed between units in relative transplantation rates. In Spain, which is a country with a high rate of deceased donor transplantation and therefore a country with arguably conservative attitudes to live donation, 60% of patients consider that the time on the waiting list is too long; yet, as many as 59% of patients claim to not have any information about living donor kidney transplantation. In the same study, more than 55% of health professionals consider nephrologists as the people that must inform the patients and family about living kidney donation, and interestingly, the youngest workers in transplant units in Spain are seen as the individuals most likely to provide the leadership for promoting for this type of kidney donation as a necessity, given the deceased donor organ deficit. Although unadjusted data, as presented here, have some potential limitations particularly based around the lack of precise data concerning the patient cultural mix, co-morbidities and/or socioeconomic status representing the base from which different units draw patients for their ESKD programs, the overwhelming majority of patients with ESKD in Victorian and Tasmania are Caucasian and no meaningful differences in racial or cultural mix or socio-economic

Non‐heart–beating donors

(Suggestions are based on Level III and IV sources) • Non-Heart Beating (NHB) donors should be considered as an extra source of deceased donor kidneys for transplantation, with acceptable patient and graft survival, in spite of an increased incidence of delayed graft function. • Results using kidneys from NHB donors may be improved by using ‘controlled’ donors younger than 60 years of age and by minimising warm and cold ischaemic times (? use kidneys locally). • Transplant Centres are encouraged to develop protocols which satisfy local and regional ethical and legal requirements. • All NHB donation procedures occur as an emergency and require a team including transplant co-ordinators and surgeons available urgently 24 hours a day.