open access: Nature Reviews: Key Advances in Medicine

have not been compared systematically to
the cost of remaining on dialysis. In addition,
this study compared patient survival
with living donor transplantation following
desensitiza tion with those accrued on
the waitlist. Whether these encouraging
observa tions could extend to deceased
donor transplantation after successful
desensitization remains to be seen.
African Americans are at increased risk
of end-stage renal disease compared with
white individuals. Recent studies suggest an
association between variants of the apolipoprotein
L1 gene (APOL1) and nondiabetic
nephropathy among African Americans. 5
In a single-center study, kidneys from
African American deceased donors with
two APOL1 risk variants were more likely to
fail (HR 3.48, P = 0.008) than kidneys from
individuals with one or no APOL1 risk variants.
6 These associations outweighed the
risk of graft loss associated with African
American ancestry. This study highlights
that transplant outcomes are more likely to
be based on biology than on arbitrary and
often culturally based definitions of race.
Whether or not donor genotype or donor–
recipient genotype interactions influence
transplant outcomes through nonimmunological
mechanisms demands confirmation.
More importantly, the application of these
associations to improve matching of donors
and recipients in organ allocation schemes
merits further study.
Successful transplantation in the clinical
arena is inseparable from the pharmacopeia
that facilitates successful transplantation.
Immunosuppressive drugs are associated
with well-known immunological and nonimmunological
adverse effects. However, it
is increasingly apparent that a small number
of recipients of renal and liver allografts
continue to have excellent graft function
many years (sometimes decades) after
stopping immunosuppression. Such individuals
are described as being operationally
tolerant. A unique B-cell expression signature
associated with increased numbers of
naive and transitional B cells in peripheral
blood has been described in operationally
tolerant kidney transplant recipients. 7
A recent study comparing character istics
of liver and kidney transplant recipients
who are operationally tolerant showed
that the gene-expression signatures of
peripheral blood mononuclear cells in
these individuals was very different, with
no significant detectable overlap between
their immuno phenotypic profiles. 8 By contrast,
tolerant and non tolerant liver recipients
had similar peripheral blood B-cell
phenotypic markers. 8
‘‘ ...transplant outcomes are
more likely to be based on biology
than on arbitrary ... definitions of
race
It is important to note that the studies
discussed above represent associations and
do not imply causal relationships. Patients
who maintain excellent graft survival
despite discontinuing immuno suppression
might differ considerably from those who
reject under similar circumstances; findings
drawn from operationally tolerant
individuals could therefore be affected
by survivorship bias. Whether genomic
and immunophenotypic markers associated
with prolonged discontinuation of
immuno suppression and excellent graft
survival could be identified prospectively
and enable programmed discontinuation
of immunosuppression in selected recipients
earlier in the course of transplantation
deserves further systematic study.
Extended criteria donor (ECD) kidneys
permit successful transplantation especially
among transplant candidates with
poor expected waitlist survival, such as the
elderly and those with diabetes. 9 However,
delays in the placement of ECD kidneys are
associated with increased cold ischemia
times (CITs) and a high rate of discard of
such organs. A recent study using data from
the Scientific Registry of Renal Transplant
Recipients examined the effect of increasing
CITs on graft survival among recipients
of paired kidneys (kidneys from the
same deceased donor transplanted to
two different recipients where one donor
had delayed graft function and the other
did not). 10 ’’
Longer CITs were associated
with increasing incidence of delayed graft
function. However, graft survival did not
signifi cantly differ across the range of CITs
studied. Although this study is limited by
NEPHROLOGY
its retrospective nature and is prone to
selection bias, it provides some impetus to
reconsider discard of ECD kidneys with
higher CITs and optimize ECD utilization
and acceptance.
The articles summarized above provide
food for thought and prospects for further
inquiry in coming years. We look forward
to fruitful developments in these and related
areas in clinical transplantation.
Department of Nephrology and Hypertension,
Glickman Urological and Kidney Institute, 9500
Euclid Avenue, Cleveland, OH 44195, USA
(T. R. Srinivas). Division of Nephrology,
University of Arizona School of Medicine,
1501 North Campbell Avenue, Tucson,
AZ 85724, USA (B. Kaplan).
Correspondence to: B. Kaplan
bkaplan@deptofmed.arizona.edu
Competing interests
The authors declare no competing interests.
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