Sunday, July 14, 2013

When should a Liver Transplant Recipient get a Combined Liver Kidney Transplant?

Currently there is huge variation in the number patients receiving a kidney transplant at the time of their liver transplant across the US; Combined Liver Kidney Transplant (CLK). The rate of good quality (standard criteria) kidneys being transplanted at the time of liver transplant varies from about 20% in the Midwest to about 6% in centers on the east coast, for example. The reasons for this disparity are varied and there is a real worry that many Liver transplant patients are receiving a kidney when one is not really needed. This reduces the number of good kidneys in the kidney alone pool. In 2012 liver-kidney transplants were the highest of all combined liver transplantations in the US.
Liver wait list patients are frequently very sick and renal dysfunction is common in this population of patients. Elevated creatinine can significantly raise the MELD score placing candidates towards the top of the liver wait list. There is a survival advantage of CLK vs Liver Transplant alone (LTA). This puts pressure on physicians and surgeons to consider transplanting a kidney with the liver. There may also be financial and statistical reasons for a center to transplant a kidney with a liver. The outcome data favoring CLK over LTA in renal failure patients is all retrospective, non-randomized and does not take into account the cause of peri-transplant renal failure and whether the patient truly had established ESRD or CKD4 at the time of transplant.  Another factor putting pressure on medical professionals to perform CLK transplants is the fear of ‘getting it wrong’. Survival is very poor in patients who do not recover renal function after LTA vs those who do. Currently a patient put onto the kidney alone list after LTA will have to wait the average 5 years for their kidney (average kidney alone wait list time in SE USA). Given the poor outcomes described by Northrup, these patients are likely to die with a functioning liver waiting for a kidney.
So can we predict who who will develop ESRD after LTA? A number of studies have looked at this using various prediction parameters.
In summary:
- RRT for less than 30days pre-LTA are likely to recover renal function
- RRT for greater than 90days preLTA are unlikely to recover
- Patients with eGFR consistently less than 30ml/min/1.73m2 (MDRD) for 90days prior to LTA had an increased risk of ESRD.
- ATN vs HRS as a cause of renal failure at time of LTA increases the risk of post LTA CKD 4/5.

So how can we improve the allocation of kidneys in CLK patients?
Dr Carl Berg is the Chairman of the OPTN/UNOS policy oversight committee, incoming UNOS Vice President and a Liver Transplant Physician at Duke University Medical Center. He recently presented a talk that highlighted the issues described above. He and others (Richard Formica and Bertram Kasiske) are working on proposals that will:
- Avoid giving kidneys to liver transplant patients with a high likelihood of renal recovery
- Provide fail-safe mechanism to provide less penalty for “guessing wrong” and not putting in a kidney with a liver
- Create a system that is not easily manipulated.

Some of the proposed ideas are as follows (these are not official UNOS/OPTN proposals but are proposals based on the expert opinions of the three mentioned authors CB, RF, BK):
Fail safe:
1) The patient receives a time credit of the 25th percentile of waiting time for the center they are listed in.
2) In addition, the patient receives credit for the time spent from transplant of the primary organ (time of arterial anastomosis to time of listing).
This time credit should encourage doctors to allow time for the kidney to recover but not discourage living donation.

Proposed criteria for offering a kidney at the time of Liver transplant
•ESRD (as defined by the Form 2728)
•Metabolic disease requiring CLK
•Acute renal failure with ≥8 weeks of dialysis
•CKD with eGFR or CrCl ≤30 mL/min
The duration and time of CKD first documentation needs to be assessed.
This is an interesting and difficult area for the transplant physician. I certainly agree that clearer guidelines are needed to ensure our limited pool of good kidneys is used wisely and no ‘game playing’ occurs. With regard to Dr Berg’s proposals; the AKI and CKD criteria are most troublesome. We all know kidneys can recover function weeks after an AKI event. Clinical diagnosis of AKI or even diagnosing CKD in these patients in difficult and requires great clinical skill from the nephrologist. Performing a kidney biopsy to gauge likelihood of recovery and cause of AKI sounds attractive but is risky and costly in this patient group.
Posted by Andrew Malone


memon said...

what about considering recipients who have received CLK, once their GFR improves and suggest their native kidneys are functioning, then donate back their transplant kidney to a potential matched recipient in a controlled environment as a Living donor.

Wael Hussein said...

Memon suggests retrieving renal transplants from patients who recover native renal function after combined liver and kidney transplants. There is a number of problems associated with this. First that comes to my mind would be the difficulty to establish the relative contribution of renal function by the native kidneys vs the transplanted kidney. Second, remember some of these patients have chronic infections, and probably malignancy risk that will be carried with the transplanted kidney. Third: remember that transplant nephrectomy is a surgically difficult procedure. Forth, even if the above problems did not exist, the most important issue would be the ethical problem of having to take this transplant recipient back to the operating room to perform yet another surgical procedure, that carries high risk for renal impairment and potential risks to his/her life. Add to that, that no matter how much recovery there is from the native kidneys, exposure to CNI's and other potential causes of renal impairment make the presence of this already transplanted kidney a potential plus to the survival of the liver transplant recipient.

manipal said...

Thanks for sharing your perspective. Very well written and informative.