Young versus old 

Does the age of donors matter in cadaver kidney transplants ? Apparently, it does.

Kidneys from older cadaver donors (over age 55) carry with them the problems of nephron loss associated with ageing and an increased susceptibility to early injuries associated with brain death, ischemia and rejection. These early injuries further shorten the useful life of older kidneys. Of the 35000 cadaver kidneys transplanted in the U.S. between 1994 and 98, 15% were from donors over the age of 55. One third of these grafts were lost within 3 years. The half-life for older kidney grafts that survived the first year was 6.1 years compared with 11.1 years when  the donor was under age 55. The long term survivals of these sub-optimal kidneys were clearly compromised but early events bearing on their survival as well. If the kidney functioned immediately and there was no early rejections, 3-year graft survival was 75% and the graft half-life was 5 years. The incidence of delayed graft function increased from 15% of 20 year old kidneys to 40% when the donor was over 60 and with prolonged cold ischemia time, the incidence of DGF was as high as 60% for older kidneys.About 45% of older kidney failures were attributed to chronic rejection, compared with 33% of those among recipients of younger donor kidneys. 

The challenge, therefore is to impove long-term survival of older cadaver kidneys, and devise methods to evaluate the functional reserve of older kidneys, reduce early injuries, minimize ishchemia and avoid young or immunologically high-risk recipients.- J. Micheal Cecka, UNOS Scientific Renal Transplant Registry, UCLA immunogenetics centre, Los Angeles, CA,USA.

Mycophenolate mofetil is safe and improves longterm graft survival in kidney transplant recipients

A clinical pilot trail was performed at the medical centre, University to Munich, Germany to evaluate the safety and efficacy to Mycophenolate Mofetil (MMF) monotherapy over Calcincurin-inhibitor (CNI) monotherapy in kidney transplant recipients. The aim was to avoid completely, CNI associated side effects contributing to chronic renal allograft dysfunction. In the trail, 46 patients with stable renal allograft function, at least 1 year after cadaveric renal transplantation and either on cyclosporin or tacrolimus monotherapy was switched to MMF monotherapy. The mean observation period(as on August 2000) since time conversion was 22.3 ± 4.9m (17 m- 39m). In 38 patients, converson procedure turned out to be successful whereas in 8 patients, conversion was associated with treatment failure(including 5 mild acute rejection episodes). The 38 patients successfully switched to MMF- monotherapy showed significant improvement on three fronts:

1. Renal allograft function(mean serum creatinine 1.9 to 1.7± 0.5 mg%)
2. Reduction of atherogenic risk factors(hypertension from 1.4 to 0.7 drugs/pt), blood lipids, e.g., cholestrol from 223 to 199mg%, triglycerides from 186 to 159 mg%.
3. Improvement of CNI-associated clinical side effects.

   In addition, protocol biopsies performed in 16 out of 38 patients, 21.2±4.6 months after conversion revealed no signs of subclinically- ongoing acute cellular rejection processes.

The conclusion that was reached based on these long-term results of MMF-monotherapy in kidney recipients, was that a CNI-free immunosuppressive protocol may contribute to improvement of renal graft function, reduction of atherogenic risk factors(and thus to potential reduction of devolpement of auto and alloatherosclerosis)without jeopardising the allograft via induction of late acute cellular immune events.

Non Heart-beating donor kidney transplant

The remarkable success of renal transplants has led to a situation where the only constraint is the shortage of organs. In an attempt to address this shortage, doctors at the University of Leicester and Leicester General Hospital. Leicester, UK established a non heart-beating donor(NHBD) Organ retrieval programme. However, questions have always been asked about the graft survival rates from NHBD as compared to those from heart-beating cadaveric(HBD) and livng donors(LD).

The Leicester programme compared the results of kidney transplants from these 3 different categories of donors over the same eight year period.

Patients dying after failed attempts at resuscitation in the Accident Department, or after intracerebral haemorrhage anoxia, were considered as potential NHBD. After death, in-situ kidney perfusion and colling was achieved using an intra-aortic catheter inserted via a femoral artery cut down. Kidney retrieval and transplant opertaions were performed using standard technique. The median(range)warm ischaemia time for NHBD, HBD, LD transplants were 6.5, 76.3 and 93% respectively. Primary non-function occurred in 7 of 77 NHBD transplants (9%)compared to only 6/224(2.7%) HBD an d1/49(2%) LD transplants. 84% of NHBD kidney recipients required post-opertaive dialysis for a median of 19 days. The mena(SD) serum ceratinine at 12 months was 179(73)μmol/l in NHBD kidneys compared to 152(57)μmol/l for HBD kidneys and 138(44)μmol/l for LD kidneys. The actuarial 5 year graft survival rates for NHBD, HBD, LD transplants were 75, 78, 79% respectively. During the period under study NHBD organs accounted for 22% of the total renal transplant programme.

Despite being associated with poor initial graft function, the long-term allograft survival of NHBD kidneys does not differ significantly from the results of HBD and LD transplants. A definite shot in the arm for NHBD kidney transplant proponents.