ABO incompatible renal transplants:Good or bad?

ABO incompatible kidney transplantation(ABOi-KT) was previously considered to be an absolute contraindication for patients with end-stage kidney disease(ESKD) due to hyperacute rejection related to blood type barrier. Since the first successful series of ABOi-KT was reported, ABOi-KT is performed increasingly all over the world. ABOi-KT has led to an expanded donor pool and reduced the number of patients with ESKD awaiting deceased kidney transplantation(KT). Intensified immunosuppression and immunological understanding has helped to shape current desensitization protocols. Consequently, in recent years, ABOi-KT outcome is comparable to ABO compatible KT(ABOc-KT). However, many questions still remain unanswered. In ABOi-KT, there is an additional residual immunological risk that maylead to allograft damage, despite using current diverse but usually intensified immunosuppressive protocols at the expense of increasing risk of infection and possibly malignancy. Notably, in ABOi-KT, desensitization and antibody reduction therapies have increased the cost of KT. Reassuringly, there has been an evolution in ABOiKT leading to a simplification of protocols over the last decade. This review provides an overview of the history, outcome, protocol, advantages and disadvantages in ABOi-KT, and focuses on whether ABOi-KT should be recommended as a therapeutic option of KT in the future.

Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation

BACKGROUND Polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless,long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also unclear.AIM To investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation.METHODS This single-centre observational study with a median follow up of 57(31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasmaquantitative polymerized chain reaction. Patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment,rejection, renal function, urologic complications, opportunistic infections, newonset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and nephropathy.RESULTS BK-viremia was detected in 9.5% recipients. Initial viral load was high(≥ 10000 copies/mL) in 66.7% and low(< 10000 copies/mL) in 33.3% of these patients.Polyomavirus-associated nephropathy was diagnosed in 6.5% of the study population. Patients with high initial viral load were more likely to experience sustained viremia(95% vs 25%, P < 0.00001), nephropathy(92.5% vs 15%, P <0.00001), and polyomavirus-related graft loss(27.5% vs 0%, P = 0.0108) than recipients with low initial viral load. Comparison between recipients with or without BK-viremia showed that the proportion of patients with Afro-Caribbean ethnicity(33.3% vs 16.5%, P = 0.0024), panel-reactive antibody ≥ 50%(30% vs14.6%, P = 0.0047), human leukocyte antigen(HLA) mismatching > 4(26.7% vs13.4%, P = 0.0110), and rejection within thirty days of transplant(21.7% vs 9.5%; P= 0.0073) was higher in the viremic group. Five-year patient and overall graft survival rates for patients with or without BK-viremia were similar. However,viremic recipients showed higher 5-year crude cumulative(22.5% vs 12.2%, P =0.0270) and 30-d-event-censored(22.5% vs 7.1%, P = 0.001) incidences of graft failure than control. In the viremic group we also observed higher proportions of recipients with 5-year estimated glomerular filtration rate < 30 mL/min than the group without viremia: 45% vs 27%(P = 0.0064). Urologic complications were comparable between the two groups. Response to treatment was complete in55%, partial in 26.7%, and absent in 18.3% patients. The nephropathy group showed higher 5-year crude cumulative and 30-d-event-censored incidences of graft failure than control: 29.1% vs 12.1%(P = 0.008) and 29.1% vs 7.2%(P <0.001), respectively. Our multivariable model demonstrated that Afro-Caribbean ethnicity, panel-reactive antibody > 50%, HLA mismatching > 4, and rejection were independent risk factors for BK-virus viremia whereas cytomegalovirus prophylaxis was protective.CONCLUSION Current treatment of BK-virus infection offers sub-optimal results. Initial viremia is a valuable parameter to detect patients at increased risk of nephropathy. Panelreactive antibody > 50% and Afro-Caribbean ethnicity are independent predictors of BK-virus infection whereas cytomegalovirus prophylaxis has a protective effect.