Transplant Immunology 33 (2015) 27–29

Contents lists available at ScienceDirect

Transplant Immunology

journal homepage: www.elsevier.com/locate/trim

A lesson from kidney transplantation among identical twins: Case report

and literature review☆
Zhengsheng Rao, Zhongli Huang, Turun Song, Tao Lin ⁎
Department of Urology, West China Hospital, Sichuan University, Guoxue Xiang #37, Chengdu 610041 Sichuan, People's Republic of China.

a r t i c l e i n f o a b s t r a c t

Article history: There continues to be disagreement related to the appropriate therapeutic regimen to be used when the donor
Received 22 June 2015 and the recipient in kidney transplant operations are identical twins. Here we present two cases of kidney
Accepted 15 July 2015 transplantation between identical twins. Both recipients had end-stage renal disease (ESRD) caused by primary
Available online 17 July 2015
nephropathy. We also present information gleaned from a literature review of similar cases. The first recipient
was a 26-year-old man who experienced biopsy-proven IgA nephropathy 10 months post-transplantation.
Keywords:
Kidney transplantation
Mycophenolate mofetil (MMF), angiotensin receptor blockers (ARBs), and steroids were used to reverse this
Identical twins pathologic condition. Till now, 76 months post-transplantation, the patient is stable, and the new kidney is
Immunosuppression functioning well. The second recipient was a 20-year-old woman who had hematuria and proteinuria 3 months
post-transplantation, and crescent glomerulonephritis with mild to moderate interstitial injury was proven by
biopsy 11 months postoperatively. This patient did not respond to various treatments and resumed hemodialysis
15 months post-transplantation. These case studies show that immunosuppressive therapy should be main-
tained in kidney transplant recipients who are identical twins with ESRD caused by initial nephropathy.
© 2015 Elsevier B.V. All rights reserved.

1. Introduction
Kidney transplantation is the optimal treatment choice in patients
with end-stage renal disease (ESRD). The first successful kidney trans-
plantation was performed in Boston by Joseph Murray on December
23, 1954 [1]. The recipient received a kidney from his monozygotic
twin brother, did not take immunosuppressive medications, and died
of a myocardial infarction 9 years postoperatively [2,3]. Following this
first kidney transplantation, a large number of successful renal trans-
plantations between identical twins were reported in the 1950s and
1960s [4–9].
The outcome of kidney transplantation in human leukocyte antigen
(HLA)-mismatched living and deceased-donor transplants has greatly
improved with the introduction of potent immunosuppressive thera-
pies [10]. However, the outcomes are very different for homozygous
twins. Due to the extreme genetic similarity between homozygous
twins, immunosuppressive regimens can theoretically be avoided.
However, any individual who receives a new kidney has a high risk of
the initial kidney disease returning just as much as new-onset nephrop-
athy. Furthermore, immunosuppressive regimens can treat both patho-
logical conditions [11,12]. Thus, the use of immunosuppressive
☆ No conflicts of interest among authors.
⁎ Corresponding author.
E-mail address: kidney5@163.com (T. Lin).
regimens when the donor and the recipient of the kidney transplant
are identical twins must be considered [13–16].
Here we present two cases of kidney transplantation between
identical twins, including dilemmas faced by the healthcare providers
related to determining the best therapeutic regimens. We also present
information gleaned from a literature review of similar cases.
1.1. Case 1
A 26-year-old male with ESRD was admitted to an organ trans-
plant center for a kidney transplant. Before his admission, he
underwent 1 month of hemodialysis, during which dyspnea and
orthopnea were observed. The surgery was performed on January 13,
2009, with an organ harvested from his identical twin brother, the ap-
propriateness of which was confirmed by genetic testing via short tan-
dem repeat (STR) DNA analysis. He had a normal serum creatinine level
of 116.7 μmol/L on postoperative day 2. The patient's postoperative
medications included intravenous methylprednisolone for 1 week and
subsequent oral prednisone for 1 month. A graft biopsy was performed
10 months postoperatively because of the emergence of proteinuria and
hematuria. The biopsy findings led to a diagnosis of IgA nephropathy
(Lee II–III). Subsequently, a regimen of MMF (250 mg/day), steroids
(10 mg/day), and ARBs was initiated, and the hematuria and protein-
uria gradually subsided. The patient has continued to administer

http://dx.doi.org/10.1016/j.trim.2015.07.004
0966-3274/© 2015 Elsevier B.V. All rights reserved.
28 Z. Rao et al. / Transplant Immunology 33 (2015) 27–29
MMF. No rejection episodes have been observed, and the graft has been
functioning stably for 6 years.
1.2. Case 2
A 20-year-old woman was diagnosed with ESRD. Two years later,
she underwent hemodialysis for 2 months. Subsequently, on October
28, 2011, she received a living kidney from her monozygotic twin sis-
ter, the appropriateness of which was confirmed by STR DNA analy-
sis. After transplantation, both intravenous methylprednisolone and
oral prednisone were administered for 1 week. At 3 months, hematu-
ria and proteinuria were observed, and her creatinine level rose to
150.7 μmol/L. A relapse of the nephropathy was suspected, but the
patient refused biopsy because of personal reasons. Then tacrolimus
(Tac), MMF, and steroids were administered. However, her condition
worsened; her creatinine increased to 192 μmol/L, and obvious gross
hematuria was observed 11 months postoperatively. A graft biopsy
at 12 months showed crescent glomerulonephritis with mild to
moderate interstitial injury. Thereafter, due to a repeating increased
level of creatinine, a sequential treatment including methylprednis-
olone (200 mg IV/day for 5 days), cyclophosphamide (0.2 g every
other day), and pure ultrafiltration was administered over the course
of three hospitalizations in the next three months. However, these
interventions failed to stop the progression of the disease. Due to the
deteriorating graft function, she resumed hemodialysis 15 months
post-transplantation.
2. Discussion
Whether immunosuppressive therapy is needed and how long it
should be maintained post-kidney transplantation among monozygotic
twins remain controversial. Theoretically, identical twins are 100% ge-
netically similar [17], but we cannot overlook the effect of intrauterine
gene mutations that may cause phenotypic and genotypic divergence
between monozygotic twins. In addition, the main arguments against
immunosuppressive therapy focus on the side effects, including hyper-
tension, diabetes, infection, bone disease, nephrotoxicity, and lack of
effectiveness in stopping the recurrence of the original nephropathy
or new-onset kidney diseases [18–21].
The literature supports the view that not all such patients need im-
munosuppressive therapy [20,22,23]. Kessaris et al. [20] retrospectively
analyzed the outcomes in 120 cases of renal transplantation in twins in
the United Sates and did not find a significant difference in the 5-year
graft survival rates between recipients who received immunosuppres-
sive therapy (n = 82) and those who did not (n = 38) (93.9 and 84%,
respectively, log rank; P = 0.12). Of the 82 patients who received
immunosuppressive therapy, 29 received maintenance therapy and
had an original disease that could be treated with immunosuppressive
therapy. No significant difference in graft survival was found between
this group and the other 53 patients who received immunosuppressive
therapy (P = 0.58). Krishnan et al. [22] performed a retrospective anal-
ysis using the Organ Procurement and Transplant Network (OPTN)
database. After observing data from 1987 to 2006, they identified 194
possible identical twin transplantations based on age, gender, race, eth-
nicity, blood type, and HLA match. They found that the percentages of
these patients not receiving immunosuppressive therapy at discharge,
1 year, and 3 years postoperatively were 28.9% (n = 56), 66.1% (n =
109), and 66.7% (n = 88), respectively. The use of immunosuppressive
therapy did not significantly affect either patient or graft survival until
5 years post-transplantation.
However, Kim et al. [19] challenge this view, proposing that the risk
of graft failure in identical twin renal transplant recipients may increase
with the withdrawal of immunosuppressive therapy. They reported on
three identical twin transplant recipients whose primary renal disease
was chronic glomerulonephritis and who did not receive maintenance
immunosuppressive therapy. One of these patients had IgA nephropathy
with proteinuria (total 24 h urine protein: 0.32 g) 41 months after
discontinuing immunosuppression and was cured after the adminis-
tration of ARBs. Another patient was diagnosed by biopsy with rapid-
ly progressive glomerulonephritis 28 months after discontinuing
immunosuppressive treatment and resumed hemodialysis 42 months
after immunosuppressive therapy was withdrawn. The third patient
had biopsy-proven focal segmental glomerulosclerosis (FSGS) 8 years
after discontinuing immunosuppressive therapy and then underwent
peritoneal dialysis.
In our cases, the transplant appropriateness of both monozygotic
twins was confirmed by genetic testing via STR DNA analysis. Both of
the recipients were diagnosed with chronic glomerulonephritis pre-
transplantation. However, it was difficult to differentiate the recurrence
of the original kidney disease from new-onset nephropathy in the grafts
because the primary renal diseases were unknown because the native
kidneys had not been biopsied. In the first case, we succeeded in
treating the patient with ARBs and immunosuppressive therapy. His
proteinuria and hematuria markedly decreased, and he has maintained
stable renal function for 6 years. In case two, immunosuppressive ther-
apy was withdrawn early after transplantation and was not resumed
until hematuria and proteinuria were detected. However, treatment
with strong immunosuppressive agents that are usually used to slow
the rapid progression of acute glomerulonephritis failed. Thus, it is
clearly important to know the primary disorder in kidney transplant re-
cipients' native kidneys, particularly if the recipient is an identical twin.
In conclusion, immunosuppressive therapy for identical twins re-
ceiving a kidney transplant presents unique challenges. Multiple factors
must be considered before immunosuppressive therapy is discontinued,
including the recipient's primary diseases, transplant history, postoper-
ative course, and immunization status.
Contribution of the authors
Zhengsheng Rao: performed the research/study, collected the data,
analyzed the data, and wrote the paper.
Zhongli Huang: collected the data, analyzed the data, and wrote the
paper.
Turun Song: performed the research/study, collected the data, and
analyzed the data.
Tao Lin: designed the research/study and edited the manuscript.
Acknowledgments
No funding supported.
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