Caliann T. Lum

Transplantation of the adult kidney into the very small child: Long-term outcome

Adult kidneys were transplanted into 12 children weighing between 5,400 and 8,800 gm. Ten received parental and two received cadaver grafts. Ten of the 12 children are alive 18 months to 9 years post transplant; eight have their original grafts and two required retransplantation-their original grafts were lost at 4 and 9 years because of chronic rejection. All but these two surviving children had normal or accelerated growth rates despite growth retardation prior to transplant. All children evidenced moderate to severe delay in psychomotor development prior to transplant. Seven of the ten survivors now have normal psychomotor function. Two are behind in school, and one with a degenerative central nervous system disease prior to transplant remains profoundly retarded. We conclude that because of donor availability, capacity for good donor-recipient matching, and minimization of time on dialysis, transplantation of adult kidneys into pediatric patients is preferable to awaiting the relatively uncommon pediatric cadaver donor. We further conclude that the procedure is warranted.

Transplantation of the adult kidney into the very small child: Technical considerations

Transplantation of adult kidneys into very small children is not performed in most centers because of concerns regarding the technical difficulty of the procedure. Advantages of the procedure include the possibility of living related donor transplantation and the increased availability of adult donor kidneys as compared with pediatric cadaver donor kidneys. We have transplanted adult kidneys into 12 children aged 11 months to 3.5 years who weighed 5,400 to 8,800 g. Ten children received living related donor and two cadaver donor grafts. Herein we describe in detail the pretransplant management, surgical strategies, intraoperative management, surgical techniques, and postoperative management which we use for transplantation of adult kidneys into very small children. Intraoperative and postoperative complications have been described to illustrate the evolving clinical principles in this area. Since 10 of the children are presently alive, 8 with their original grafts, 16 months to 9 years after transplantation, we advocate this approach for suitable small children with terminal renal failure.

Kidney allograft survival in dogs treated with total lymphoid irradiation.

Total lymphoid irradiation (TLI) is immunosuppressive and, in rodent, can induce a state where transplantation of allogeneic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. We attempted to apply this treatment to a large animal model. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950-3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned (serum creatinine level less than 2.0 mg/dl) for a mean +/- (SE) of 4.7 +/- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15-76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemagglutinin and in mixed lymphocyte culture was suppressed for at least on month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients.

Results Of Kidney Transplantation In The Young Child

One hundred and two consecutive first kidney transplants were performed in children 10 years old and younger (47 ≤ 5 years old) at the University of Minnesota between June 1963 and April 1981. Five infants under 1-year old received transplants, two of whom are alive and well. The mean age was 6 years and mean weight was 16 kg. The most common primary renal diseases were congenital hypoplastic-dysplastic kidneys (25.5%), congenital nephrosis (20%), and glomerulonephritis (16.5%). Statistical analyses of cumulative patient and graft survival were based on the results of 88 first kidney transplants performed in children 1 to 10 years old since 1968 when medical management, patient selection criteria, surgical technique, and immunosuppression protocols were standardized. Patient survival was 72%. Twenty-six percent received transplants at least twice (23 of 88), one-half of whom still have functioning second grafts. Mean intraoperative systolic blood pressures were significantly lower in children who received intraperitoneal versus extraperitoneal grafts. No differences in central venous pressure were observed. The mean blood pressure drop at the time of revascularizing the kidney did not appear to be directly related to the incidence of postoperative acute tubular necrosis (ATN). Most patients underwent splenectomy prior to or at the time of transplantation. With the use of prophylactic antibiotics, splenectomy was not a single determining factor in deaths from sepsis. Technical complications were few (four renal artery stenosis and six ureteral revisions). Results of parent to child kidney transplants in the child under 10 did not differ significantly from those results seen in an older (17 to 49) parent to child group who received transplants at this same center.

Prolongation of mouse and rat pancreatic islet cell allografts by adenosine deaminase inhibitors and adenine arabinoside

Abstract Two adenosine deaminase inhibitors, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and 2-deoxycoformycin (2dCF) were evaluated for immunosuppressive properties in mouse and rat pancreatic islet cell allograft models. In the mouse model, administration of EHNA alone prolonged the survival of islet allografts. In the rat, neither EHNA or 2dCF alone permitted islet allograft survival. However, 2dCF, in combination with the deoxyadenosine analog adenine arabinoside provided significant rat islet allograft survival during a limited 8-day period of study.

Inhibition of human T-cell rosette formation by the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA)

Abstract Mononuclear cell surface markers from normal human volunteers were tested in the presence of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA). Only the T-cell surface marker, formation of rosettes with sheep red blood cells, was significantly inhibited by concentrations of EHNA in a dose-dependent manner. Metabolic compartmentalization of adenosine compounds at the site of nucleoside transport across the cell membrane may play an important role in determining T-cell rosette formation and whether or not the blastogenic response of these cells to environmental mitogens will occur.

Inhibition of PHA and NalO4 mitogenesis by the adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and 2-deoxycoformycin (2-dCF)

Abstract Two adenosine deaminase inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and 2-deoxycoformycin (2-dCF), significantly inhibit the normal mitogenic response of dog peripheral blood mononuclear cells to phytohemagglutinin (PHA) and sodium periodate (NaIO 4 ) oxidation. The addition of excess PHA does not reverse the inhibitory effects of EHNA on the normal PHA response. However, it was further observed that if EHNA (10 −3 , 10 −4 M ) or 2-dCF (10 −3 M ) were added to fresh cultures of murine P388 leukemia cells or Novikoff rat hepatoma cells, cellular proliferation, in general, was markedly inhibited. We then pretreated dog cells with 2-dCF and observed that even a brief exposure of cells to this compound was sufficient to inhibit the increased [ 3 H]thymidine uptake of these cells in response to PHA or NaIO 4 treatment. In contrast, similar pretreatment of Novikoff or P388 cells did not alter the normal logarithmic growth phase. Therefore, we conclude that EHNA and 2-dCF may have an overall inhibitory effect on cellular proliferation when continuously present in cultures of dog mononuclear cells, P388 mouse leukemia cells, and Novikoff rat hepatoma cells. However, unlike continuous cell lines which grow normally after pretreatment with 2-dCF, it appears that there is a specific requirement for normal ADA function early in the initiation of DNA synthesis in dog cells which are responding to the nonimmunologic mitogenic stimulation of PHA and NaIO 4 .