The American Society of Transplantation

The principles of organ preservation are flushing, cooling, and pharmacologic intervention. University of Wisconsin (UW) solution is currently considered the standard preservation solution for livers, kidneys, and pancreases. The osmotic concentration is achieved by the administration of metabolically inert substrates like lactobinat and raffinose. Other components include hydroxyethylstarch as a colloid carrier, oxygen radical scavengers, glutathione, allopurinol, and adenosine. Histidine-Tyrptophan-Ketoglutarate (HTK) solution is another option which has shown similar safety and efficacy at least for lower cold ischemia times. Its contents include histidine, mannitol, tryptophan and alpha-ketoglutaric acid. It also contains low concentrations of sodium, potassium, and magnesium. Histidine serves as a buffer, and tryptophan, histidine, and mannitol act as oxygen free-radical scavengers. There is some evidence that using cold lactated Ringers with additives can be safely used for short-term cold preservation of kidneys from living renal donors and is a cost-effective option but only in that circumstance.

In the current age, the empiric treatment of acute rejection – that is without the benefit of the gold standard: kidney transplant biopsy – is not optimal standard of care with the exception of situations in which the risk-benefit ratio is deemed to be unacceptable.

The diagnosis of antibody-mediated rejection (AMR) requires the presence of light microscopic changes that are well characterized, evidence of antibody activation – C4d deposition in the peritubular capillaries, and detectable donor specific antibody in the recipient serum.

Although one can argue that these criteria need not to be present concomitantly for a patient to have AMR, pursuing the accurate diagnosis is essential to guide therapy appropriately; and empiric therapy should be discouraged.

Rituximab is an expensive chimeric antibody, which efficacy in the treatment of antibody-mediated rejection remains to be proven, and with potentially severe side-effects including infection, prolonged late hypogammaglobulinemia, and neutropenia among others. Thus while using rituximab in AMR can be argued in terms of efficacy, its use without a proven diagnosis is not acceptable.

The use of generic tacrolimus poses an interesting dilemma to the transplant community. As opposed to mycophenolate, a non-nephrotoxic drug with excellent and for most predictable bioavailability, tacrolimus has a narrow therapeutic window, and a more variable pharmacokinetic profile. In contrast to some generic preparations of cyclosporine – no pharmacokinetic studies of generic tacrolimus have been carried out in American transplant patients. Since the Food and Drug Administration only requires testing of generic drugs in healthy subjects for approval, performance of clinical pharmacological studies in our transplant patients will not happen.

The paucity of data upon which to base a safe decision making is particularly concerning in the light of a post-hoc analysis of a 3-year randomized, open-label controlled study conducted in Mexico and presented at the 22nd International Congress of the Transplantation Society in August 20081. In this study, primary kidney transplant recipients treated with a generic tacrolimus preparation (Tenacrine) had a greater incidence of acute rejection than their counterparts treated with Prograf. Mean tacrolimus blood levels were lower in patients treated with the generic form at 3, 6, and 9 months post-transplant when compared with baseline (P < 0.05)1.

Notwithstanding our trepidation, in the current environment of health care reform and cost-containment, private insurance companies will soon impose high co-pay rates on Prograf thereby limiting its access to our patients, and physicians will be left with few options other than a close follow-up of those patients switching agents and hope for the best possible outcome.

Reference:
1)Holm Corzo A et al: A Post-Hoc Analysis of the Safety and Efficacy of Tacrolimus (Prograf) Versus a Generic Formulation of Tacrolimus (Tenacrine) as Primary Immunosuppressive Therapy in LRD and CAD Adults and Pediatric Renal Transplant Recipients [Mini-Oral Session 18 WMO18]
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No randomized studies directly comparing 450mg and 900mg of valganciclovir exist to the best of my knowledge. However, there is data supporting the efficacy of both doses which suggests that the lower dose is probably sufficient in most situations. At our institution, we provide 900mg only to our D+R- liver transplant recipients. All other liver and kidney recipients (except D-R-) receive 450 mg (or adjusted for renal function). Clinicians should be aware of two issues. First, late-onset CMV disease after prophlyaxis has been discontinued is a signficant problem in D+R- patients. Second, dosing of valganciclovir should be readjusted in renal transplant recipients with fluctuating renal function. Most importantly, as renal function improves the dose should be increased to avoid suboptimal prophylaxis and breakthrough CMV disease. Leukopenia can be addressed by either decreasing the dose or providing GCSF.

Directed donations challenge the traditional construct of altruistic donation

In your case, I am not sure how the deceased individual provided consent for this (was this part of a living will?).

In any regard there is policy in the United States regarding directed deceased donation.

The following in formation is taken directly from UNOS.

“Directed donation is a request made by a donor or donor family to transplant a specific recipient. This practice is legally authorized by the Uniform Anatomical Gift Act (UAGA) and by most state anatomical gift laws, which use the UAGA as a guide. (A few state laws are silent on directed donation but do not specifically disallow the practice.)

The policy of the national Organ Procurement and Transplantation Network (OPTN), operated by United Network for Organ Sharing (UNOS) under federal contract, recognizes directed donation as long as the agencies involved take steps to verify the medical suitability of the organ offer for the specified recipient. The Federal regulation that guides the OPTN (the OPTN Final Rule) expressly allows directed donation to a named individual.

In recent years, at least 100 deceased donor transplants each year have occurred through directed donation. Such requests occur most frequently when the donor or donor family either are related to the recipient or know the recipient personally. Past instances of directed donation that have resulted in media coverage include a daughter-to-father heart transplant and a heart transplant from a church member to the church’s pastor. In many instances, only one organ from a deceased donor is directed to a specific recipient; other organs from the donor are allocated according to OPTN policy."

In England, Wales and Northern Ireland, the Human Tissue Act 2004, and in Scotland the Human Tissue (Scotland) Act 2006, are both silent in this regard. Although so-called conditional donation, donation to (or perhaps withheld from) a specific class, has been outlawed as a product of guidance issued by the Secretary of State for Health issued in the wake of the controversial incident occurring in the North of England in 1998, its intended application to ‘directed’ donation is less certain.

In Canada, there are very few examples of directed deceased donation that I am personally aware of.

Most of the American cases appear to have a clear relationship between the donor and the recipient. Although establishing the nature of a relationship can be very difficult, it is clearly desirable. Any suggestion of either coercion or payment should preclude a directed donation.