RENAL TRANSPLANTATION: SINGLE OR DUAL FOR DONORS AGING ???60 YEARS?

Double Versus Single Renal Allografts from Aged Donors. Transplantation 2000; 69: 2060.Andrés A, Morales JM, Herrero JC, Praga M, Morales E, Hernández E, Ortuño T, Rodício JL, Martínez MA, Usera G, Díaz R, Polo G, Aguirre F, and Leiva O. Renal transplantation is regarded by most as the preferred treatment for chronic renal failure, it improves patient independence and rehabilitation and is more cost-effective than dialysis. However, shortage of kidney donors is still a major limitation. The imbalance between kidney demand and supply is such that in 1995 only one of seven patients on waiting list had a chance of a transplant in the United States, as compared with one of three in 1988. Expansion of the pool of available organs by a more liberal selection of potential donors may help to close the gap. With this logic, attempts have been made with the use of non-heart-beating donors, or of donors whose organs were not ideal due to concomitant hypertension, diabetes or hepatitis C. Kidneys have occasionally been used even after very prolonged cold ischemia time or despite evidence of anatomic abnormalities. Organs from nonideal organs, however, may have a poor outcome. When donors aging ≥60 years or with a creatinine clearance <90 ml/min are used or cold ischemia time is >24 hr, the frequency of posttransplant anuria is close to 50% and the short-term renal function is usually poor (1). Organs from very old donors or from donors with hypertension or diabetes or preexisting renal functional abnormalities tend moreover to develop proteinuria and progressive renal scarring that considerably reduces the long-term survival. Because either delayed graft function and appearance of proteinuria predict premature graft failure, this approach was abandoned by most centers. Missmatches between the number of viable nephrons supplied by single kidneys from nonideal donors and the metabolic demand of the recipients could possibly account for the poor outcome, especially when old donor kidneys are used after prolonged enough cold ischemia, which in turn further reduces the viable renal mass. Andrés and co-workers (2) quantified the degree of glomerulosclerosis, taken as an indicator of the functioning nephron mass, in kidneys from all potential donors 60 years or older, and selected for transplant only kidneys with less than 15% sclerotic glomeruli. Despite, again, the high incidence of delayed graft function, 95% of transplants were successful at 6 months. Evidence, however, that recipients of single kidneys from old donors had significantly higher serum creatinine levels as compared with recipients of ideal grafts, arises some concern that nonideal kidneys might be at increased risk of premature failure in the long-term. More encouraging were the results obtained by the same authors (2) when both kidneys from marginal donors were transplanted simultaneously into the same recipient. This approach is not novel: a retrospective analysis of uncontrolled cases (1) showed comparable renal function recovery at 6 months in recipients of dual marginal or single ideal kidneys. A prospective, case-control, multicenter study (4) has very recently documented that double transplant of marginal kidneys, kidneys from donors aging ≥60 years, selected on the basis of rigorous quantification of glomerular, vascular, tubular, and interstitial changes, offered remarkably good short-term posttransplant renal function without exposing recipients to enhanced risk of surgical complications. Findings that recipients of these kidneys at 6 months had lower serum creatinine and blood pressure values than controls, indicates that two marginal kidneys provide an adequate filtration power possibly even superior than one single ideal kidney: this, in turn would predict good long-term results. Actually, a very recent comparative analysis of the Dual Kidney Registry and the UNOS Scientific Registry found that dual versus single grafts from marginal donors had a remarkably higher 3 year survival. On the basis of this study, a policy of using donors ≥60 years of age with creatinine clearance <90 ml/min and history of hypertension as a dual transplant (5) was recommended. Andrés and co-workers (2) considered for the dual transplant very old donors (aged up to 89 years), provided they had less than 50% glomerulosclerosis. Finding that short-term outcome of double transplants from marginal donors was comparable to that of single transplants of an ideal kidney, at least in the short-run, indicates that kidneys that would have been otherwise discarded can actually provide enough renal function to an average recipient if transplanted together. An open issue remains long-term survival of transplants done by the simultaneous dual marginal kidney procedure. The remarkably low incidence of acute rejections and delayed graft function observed in all published series (1–5) would indeed predict excellent long-term outcomes. Andrés and co-workers (2) have used pretransplant biopsy scores to establish whether organs could be used alone or as dual kidneys to the same recipient. One may wonder whether such decision can in fact rest on the histology score, because a few milligram tissue might not represent whole kidney structural changes, in circumstances of random distribution of lesions. However, finding of a strong correlation in vascular, glomerular, and tubulointerstitial changes between biopsy and autopsy of kidneys from old donors originally considered for single transplants and then discarded for various reasons ( Table X, Mazzucco G, personal communication) supports the predictive value of pretransplant biopsy. TABLETable 1: Renal biopsy and autopsy scores in kidneys from marginal donors not used for transplantationAttempts to expand the donor pool with marginal kidneys highlights the need of titrating nephron mass supply to recipient metabolic demand as a possible effective way to prolong long-term organ survival, still the most challenging task of transplant medicine. Efforts to enhance long-term survival is certainly a better strategy than increasing transplant activity, in that it would limit the costs of readmission to dialysis and the need of second transplants (transplant failure is, after diabetic nephropathy, the most common cause of end stage renal failure in the United States). From the study of Andrés and co-workers (2) it should be also noted that during the period in which the program was performed only 18% of donors aged older 60 years have been discarded as compared with 35% in a comparable period before the protocol was started. Transplanting kidneys from very old donors is therefore feasible and offers positive prospects of overcoming the current shortage of donor organs. In addition to expanding the donor pool, kidneys from very old donors represent a new opportunity for old or relatively old people now on chronic dialysis to improve the quality of their remaining years of life.