Unrecognized acute phosphate nephropathy in a kidney donor with consequent poor allograft outcome.

Acute phosphate nephropathy following a large phosphate load is a potentially irreversible cause of kidney failure. Here, we report on the unfavorable graft outcome in two recipients of deceased donor kidneys from a donor who had evolving acute phosphate nephropathy at the time of organ procurement. The donor, a 30-year-old with cerebral infarction, developed hypophosphatemia associated with diabetic ketoacidosis and was treated with intravenous phosphate resulting in a rise in serum phosphorus from 0.9 to 6.1 mg/dL. Renal biopsies performed on both recipients for suboptimal kidney function revealed acute tubular injury and diffuse calcium phosphate microcrystal deposits in the tubules, which were persistent in subsequent biopsies. A retrospective review of preimplantation biopsies performed on both kidneys revealed similar findings. Even though initial renal histology in both recipients was negative for BK virus, they eventually developed BK viremia with nephropathy but both had a substantive virologic response with therapy. The first patient returned to dialysis at 6 months, while the other has an estimated glomerular filtration rate of 12 mL/min, 17 months following his transplant. We conclude that unrecognized acute phosphate nephropathy in a deceased donor contributed substantially to poor graft outcome in the two recipients.

Expectations and outcomes in organ transplantation.

Research is needed on the frequency of bad outcomes in transplantation. Allocation policies and professional or institutional self-interest may affect the incidence of bad outcomes, and the need for reform is stressed. Transplant recipients who have had a bad outcome often continue to receive aggressive care. The humanistic care of patients having bad outcomes requires attention to advance directives, discussion with patient and family of alternatives to aggressive treatment, and provision of an option for home hospice care. Finally, it must be reemphasized that the average typical good outcome is extraordinarily good, restoring function of a vital organ, extending and improving quality of life, and sometimes restoring near-normal health. In no way should the fact of bad outcomes reduce our commitment to producing good outcomes.

Renal transplantation without sutures using the vascular clipping system for renal artery and vein anastomosis--a new technique.

A cadaveric renal transplant was performed on a 63-year-old woman. The donor renal artery and vein were anastomosed to the recipient external iliac vessels using the vascular clipping system. These vascular anastomoses were performed with four stay sutures and several clips for each anastomosis, without a continuous vascular suture. The time taken was 8 min for each anastomosis. There were no postoperative complications and the patient went home after 6 days in the hospital. At 1 month follow-up her serum creatinine was 1.3 mg/dl. We conclude that cadaveric renal transplantation can be performed using clips for the vascular anastomoses. This technique permits an expeditious, interrupted anastomosis. Since the arcuate legged clips are nonpenetrating, there is minimum trauma to the vascular intima. In pediatric transplantation this interrupted technique may be of special importance, since it should allow the anastomoses to grow with time. The ability to quickly perform this type of anastomosis may reduce warm ischemia time as well. The safety and technical ease of this technique should allow its application in the anastomosis of other tubular structures as well. This might further improve the currently excellent outcomes of solid organ transplantation.

The use of granulocyte colony-stimulating factor after liver transplantation.

Granulocyte colony-stimulating factor (G-CSF) increases the number of circulating granulocytes and decreases TNF production while improving survival in sepsis models. To study the effects of G-CSF administration on sepsis and rejection, 37 primary liver allograft recipients received intravenous recombinant human G-CSF (rhG-CSF; 5-10 micrograms/kg/day) for the first 7-10 days following transplantation, targeting a blood absolute granulocyte count of between 10,000 and 20,000 cells/mm3. These recipients were monitored prospectively for sepsis and rejection, as were the previous 49 primary liver allograft recipients who did not receive G-CSF. Both groups utilized identical protocol immunosuppression and standardized diagnosis and treatment of sepsis and rejection. Univariate and logistic regression analysis of risk factors for sepsis and rejection revealed no difference between the two patient groups. G-CSF-treated patients developed an increased absolute granulocyte count over time (P < 0.0001, repeated-measures analysis of variance). G-CSF-treated patients had a decreased number of sepsis episodes per patient (0.92 +/- 1.5 vs. 2.18 +/- 2.8, P < 0.02, t test), and a lower percentage of sepsis-related deaths (8% vs. 22%, P < 0.04, chi-square test). The incidence of acute rejection was decreased in the G-CSF-treated group (22% vs. 51%, P < 0.01, chi-square test). These pilot data support further investigation into G-CSF's favorable effects on sepsis and rejection.

An evaluation of leflunomide in the canine renal transplantation model.

Leflunomide is an isoxazole with newly discovered immunosuppressive properties. Its mechanism of action operates later in the cell cycle than cyclosporine and appears to interfere with lymphocyte IL-2 responsiveness. With the encouraging results from in vitro and small-animal studies, we subjected leflunomide to the rigorous canine renal transplantation model in a dose response protocol. Thirty-eight female mongrel dogs underwent renal transplantation and bilateral nephrectomy. Immunosuppression was stratified from controls with no immunosuppression to monotherapy with leflunomide at 2, 4, 8, and 16 mg/kg/day given orally and in a combination therapy with cyclosporine. To evaluate its toxicity while maintaining a low constant blood level, eight dogs were treated by continuous intravenous infusion at doses of 2, 4, 6, and 8 mg/kg/day. The mean survival time for nonimmunosuppressed controls (n = 2) was 9 days, leflunomide 2 mg/kg/day (n = 2) was 9 days, leflunomide 4 mg/kg/day (n = 4) was 16 days, leflunomide 8 mg/kg/day (n = 5) was 28 days, leflunomide 16 mg/kg/day (n = 7) was 21 days. Cyclosporine alone at 10 mg/kg/day (n = 4) resulted in a mean survival time of 13 days. The mean survival time with the combination of cyclosporine 10 mg/kg/day with leflunomide 4 mg/kg/day (n = 6) was 68 days. The mean survival time for continuous intravenous leflunomide 2 mg/kg/day (n = 2) was 10 days; for leflunomide 4 mg/kg/day, 20 days; for leflunomide 6 mg/kg/day, 14 days; and leflunomide 8 mg/kg/day, 21 days. The mean serum trough levels of leflunomide ranged from 10 micrograms/ml at the 2 mg dose to 55 micrograms/ml for the 16 mg dose, levels that have been well tolerated in man. Leflunomide at 16 mg/kg/day reliably prevented acute allograft rejection, but the dogs died of inanition with normal renal function. Leflunomide at a nontoxic dose of 4 mg/kg/day extended survival to 16 days, but all dogs died of rejection. A combination of inadequate doses of leflunomide (4 mg/kg/day) and cyclosporine (10 mg/kg/day) resulted in all animals having normal renal function and weight for > or = 30 days. Even at a high dose of 16 mg/kg/day, no viral or bacterial infections were noted. These observations in a canine system add to the growing enthusiasm for the evaluation of leflunomide in human transplantation.