but that extended altruistic donation chains have been performed. Despite such inno‑ vative approaches, however, many highly sensitized patients still cannot receive a compatible transplant.
The development of effective antiretroviral therapies has dramatically improved the life expectancy of patients with HIV infection;
‘‘
...elaborate donation ‘chains’
require elegant and quite complex
algorithms
’’
Box 1 | Advances in renal transplantation in the past decade
■ Only a few clinical studies of tolerance in transplantation have been performed to date, but mechanistic insights into tolerance are increasing
■ The new US kidney allocation system aims to pair the best kidneys to patients with the longest expected survival
■ Transplantation of patients with HIV infection has become increasingly common ■ Great progress has been made in molecular diagnosis of graft rejection, but the findings
require robust validation
■ Biomarker development has been slow and meticulously performed studies have not been universally adopted by the transplantation community
■ The co‑stimulatory blocker belatacept is the first biologic agent approved for maintenance therapy for the prevention of graft rejection, but adoption for newly transplanted patients has been slow
■ The pathology of graft loss is coming under greater scrutiny and new paradigms of loss of allograft function are emerging
however, many HIV infected individuals develop end‑stage renal disease (ESRD). It had long been held that the immunosuppres‑ sion necessitated by transplantation would be dangerous to these individuals and not provide an adequate risk‑to‑benefit profile. In 2010 Stock et al. reported on an NIH sponsored multi‑centre trial of kidney trans‑ plantation in HIV patients with ESRD. 150 patients were enrolled with 3‑year patient and graft survival of 88% and 73.7%, respec‑ tively.8 Although these results are slightly
inferior to transplantation outcomes in recip‑ ients without HIV infection, this study pro‑ vided hope to individuals with HIV infection and resulted in the formation of guidelines to help improve results in the future.
Belatacept is the first biologic agent to be approved by the FDA for main tenance therapy for the prevention of acute rejec‑ tion.9 This drug offers the potential promise
of avoiding toxicities associated with calci‑ neurin inhibition, while maintaining adequate immunosuppression. Early trials showed improved glomerular filtration rates, but a potential signal of a greater risk of Ebstein Barr‑related lymphoma. The role of belatacept in kidney transplantation remains to be defined.
Although the prevention of acute rejec‑ tion has been the subject of numerous inquiries, the aetiology of graft loss has only been a major focus over the past decade.
EL‑Zoghby and colleagues looked at the pathology of patients who suffered graft loss and defined three major aetiologies:10
antibody‑associated glomerular lesions, interstitial fibrosis with tubular atrophy and recurrent glomerular disease. Interestingly calcineurin inhibitor toxicity was not a cause of late graft loss. This study has revised our thinking about approaches to prolong graft survival and further studies in this area are eagerly awaited.
The papers highlighted here are a subjec‑ tive list and are in no way meant to be all inclusive. The advances in many areas of transplantation, including tolerance induc‑ tion, allocation policy, molecular diagnostics, desensitization protocols and new immuno‑ suppressive agents are illustrative of the major advances that have been made in this field over the past decade (Box 1). These advances will hopefully pave the way to more individualized approaches to the care of transplant recipients. As analytic skills catch up with technological advances, earlier and more accurate diagnostics will become more commonplace. Further approaches to decrease the toxic immunosuppressive burden will also improve the quality of life of transplant recipients over the coming decade.
Arizona State University, 550 North 3rd Street,
Phoenix, AZ 85004, USA.
doi:10.1038/nrneph.2015.159 Published online 22 September 2015 Competing interests
The author declares no competing interests. 1. Kawai, T. et al. HLA‑mismatched renal
transplantation without maintenance immunosuppression. N. Engl. J. Med. 358, 353–361 (2008).
2. Friedewald, J. J. et al. The kidney allocation system. Surg. Clin. North Am. 93, 1395–1406 (2013).
3. Einecke, G. et al. A molecular classifier for predicting future graft loss in late kidney transplant biopsies. J Clin. Invest. 120, 1862–1872 (2010).
4. Kurian, S. M. et al. Molecular classifiers for acute kidney transplant rejection in peripheral blood by whole genome gene expression profiling. Am. J. Transplant. 14, 1164–1172 (2014).
5. Hricik, D. E. et al. Multicenter validation of urinary CXCL9 as a risk‑stratifying biomarker for kidney transplant injury. Am. J. Transplant. 13, 2634–2644 (2013).
6. Montgomery, R. A. et al. Desensitization in HLA‑incompatible kidney recipients and survival. N. Engl. J. Med. 365, 318–326 (2011).
7. Rees, M. A. et al. A nonsimultaneous, extended, altruistic‑donor chain. N. Engl. J. Med. 360, 1096–1101 (2009).
8. Stock, P. G. et al. Outcomes of kidney transplantation in HIV‑infected recipients.
N. Engl. J. Med. 363, 2004–2014 (2010).
9. Vincenti, F. et al. Costimulation blockade with belatacept in renal transplantation. N. Engl. J.
Med. 353, 770–781 (2005).
10. El‑zoghby, Z. M. et al. Identifying specific causes of kidney allograft loss. Am. J.
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