Nephron underdosing: a programmed cause of chronic renal allograft failure

The findings cited in this report suggest that renal allograft survival might be improved by matching nephron supply to recipient needs (analogous to prescription dialysis based on Kt/V). Methods for assessing functional graft capacity (ie, nephron number, filtration, or total microvascular surface area) are needed. Graft weights might serve as a useful alternative until better indices are devised. Measures for defining and possibly reducing recipient demands are also needed to preserve graft performance. Where gross imbalances between nephron supply and recipient demand are not likely to be corrected over the long term by engraftment of a single kidney, consideration should be given to dual kidney transplantation, currently feasible only from cadaveric, but eventually from xenogeneic sources as well. The predicted longer survival and avoidance of premature return to end-stage renal disease with the transplantation of two kidneys in certain conditions could render this approach more rational, both in clinical and economic terms, than single kidney engraftment for those at greatest risk for shortened graft survival. The dosing of larger numbers of nephrons might also lessen the risk of coexistent hypertension and thereby reduce the magnitude and tempo of immune injury to the graft.