Identical Twins Don't Need Immunosuppression After Transplant

Pam Harrison

November 20, 2019

Approximately half of identical twin kidney transplant recipients still received some form of immunosuppression despite the fact that they were truly monozygotic twins and didn't need any, indicates a new study looking at contemporary twin-to-twin transplants.

"Some transplant physicians are not comfortable managing a patient without immunosuppression, so they tend to give at least some form of immunosuppressant therapy," senior author Sundaram Hariharan, MD, who is the medical director of kidney and pancreas transplant at the University of Pittsburgh School of Medicine, Pennsylvania, told Medscape Medical News.

"But if you know they are identical twins, there is no need for immunosuppression," he stressed.

However, if patients have some form of glomerular nephritis as the underlying cause of their end-stage renal disease (ESRD), the fear that it "might come back into the transplanted kidney may have prompted the use of immunosuppression in some of these patients, which is fair," he noted.

However, in this particular study, there was not enough information about glomerular nephritis among twins receiving transplants to draw any firm conclusions about the benefits of immunosuppression for these patients, the investigators note.

They propose guidelines for genetic testing and continued management of identical twin transplants in their article, recently published in the American Journal of Transplantation.

There Were 143 Kidney Transplants Between Twins in Modern Era in US

Based on data from the Scientific Registry of Transplant Recipients (SRTR), 143 living donor kidney transplants were done in the United States between presumed identical twins in 2001-2017, lead author Dana Jorgensen, PhD, MPH, an epidemiologist at the University of Pittsburgh Medical Center, and colleagues found, as they set out to document twin transplants in the modern era.  

At 6- and 12-months post-transplantation, 54% and 50%, respectively, of identical twin transplant recipients were not taking any immunosuppressive medication.

Importantly, "we found similar patient and graft survival among patients not taking immunosuppression compared to those who were on immunosuppressive medications at 6-months and at 12-months post-transplant," the authors emphasize.

Also, there was no difference in risk of graft survival between those age ≥ 35 years and < 35 years at time of transplantation (P > .05), but there was a significant difference in patient survival in favor of younger patients.

No Differences in Survival Based on Glomerular Nephritis

Among the twins, 30% had glomerular nephritis as the cause of end-stage renal disease (ESRD). Of these patients, 64% were receiving some form of immunosuppression after the transplant.

And 39% of patients who were taking some form of immunosuppression did not have glomerular nephritis as the cause of their ESRD.

There were no significant differences in patient survival based on a glomerular nephritis diagnosis.

At 10 years, 97.4% of patients with underlying glomerular nephritis as the cause of ESRD were still alive, compared with 94.5% of those who did not have glomerular nephritis, the authors observe.

On the other hand, kidney graft survival rates at 10 years were significantly lower in patients with versus without glomerular nephritis (75.9% vs 87.5%; P = .06).

Thus, despite modern immunosuppressive regimens, "recurrence of native kidney disease remained an important cause of allograft dysfunction and failure in this population," the authors note.

And recurrent glomerular nephritis "is not always amenable to immunosuppressive agents," they observe.

"The role of continuing immunosuppressive agents to prevent recurrent glomerular nephritis in monozygotic twin transplants remains uncertain and is potentially dependent on the type or severity of glomerular nephritis at the time of transplant," they stress.  

"Our current analysis clearly shows a higher proportion of recipients with glomerular nephritis receiving immunosuppression after transplantation, lower graft survival among recipients with glomerular nephritis, but similar patient survival to nonglomerular nephritis cases," they conclude.

Six-Step Approach to Verify Twins Are Identical

Jorgensen says that although patients might think they are identical twins, unless they've been genetically tested, they don't know for certain.

"Maybe [this is why] doctors put these patients on immunosuppressants, just in case," she suggested.

Dizygotic or fraternal twins do not have the same DNA as their sibling, so they absolutely require maintenance immunosuppression, as do both human leukocyte antigen (HLA)-matched and -mismatched living and deceased donor kidney recipients.

Thus, the most important lesson from the study is to confirm the donor and potential recipient are, in fact, identical twins, Hariharan emphasized. This should be done initially by confirming that variables such as date of birth, sex, blood type, and HLA A, B, and DR antigens are the same.

However, as a final step, transplant physicians also need to confirm the donor/recipients' monozygotic status prior to transplantation using either 13 or 17 short tandem repeat (STR) tests for select regions on the DNA.

This can be done by any tissue-typing laboratory that performs these tests, which all US transplant centers have access to, Hariharan noted.

Panel reactive antibody screening for Class I and II antigens, as well as T- and B-cell crossmatch tests also need to be done between donor and recipient.

Following transplantation, physicians should avoid both induction antibody treatment as well as maintenance immunosuppression in patients receiving a kidney from their identical twin, unless treatment is required for other immunological diseases, such as systemic lupus erythematosus.

On the other hand, steroids may be given for 5 to 7 days following transplantation.

In the short-term, all aspects of renal function should be monitored and patients should undergo ultrasound imaging and surveillance biopsy. And high-risk recipients should also be checked for potential viral infections, such as cytomegalovirus and Epstein-Barr virus.

Safe to Withhold Immunosuppression?

For long-term follow-up of twin transplants, all aspects of renal function still need to be monitored and renal biopsies done when indicated for worsening renal function, or significant proteinuria or hematuria.

Patients should also be monitored for the development of high blood pressure, diabetes, or dyslipidemia, and treated accordingly.

"If you ask me, I'm very comfortable withholding immunosuppressants from a patient who received a kidney from their identical twin," Hariharan said in a statement from his institution.

"[And since] every transplant patient will have surveillance to quickly detect potential organ rejection, they can be put on immunosuppressants later if the need arises," he added.

Hariharan maintains a website for patients waiting for transplantation.

Am J Transplant. Published online October 9, 2019. Abstract

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