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Biomedical subjects

R B Ettenger

Publications and source records attributed to R B Ettenger.

At least 19 recordsLinked to original sources
PubMed1995

Intrarenal extramedullary erythropoiesis in renal allograft fine-needle aspirates.

Recombinant human erythropoietin (rhEPO) is widely used in patients with end-stage renal disease and occasionally in renal allograft recipients to correct anemia. Red blood cell production is markedly increased by rhEPO; however, no extramedullary erythropoiesis (EME) has been associated with this hormone. We observed intrarenal EME in five allograft fine-needle aspirates performed for reduced graft function in four patients between 3.7 and 7 weeks following transplantation. These four patients received rhEPO during dialysis and three resumed rhEPO therapy after transplantation; all four remained anemic. Donors were between 13 months and 13 years of age, with one pediatric and three adult recipients. Aspirates with apparently incidental EME contained all stages of red blood cell precursors, but these cells were not observed in corresponding peripheral blood samples. The hematopoietic cells could be readily distinguished from cells of lymphoid origin. There were no correlations between intragraft EME and aspirate or clinical diagnosis referable to renal dysfunction. Aspirates performed prior to 3.7 weeks or after 7 weeks did not demonstrate EME. These data suggest that endogenous EPO and rhEPO in anemic patients receiving pediatric renal allografts may activate red blood cell precursors in the young graft, inducing intrarenal EME. Recognition of this entity is important to distinguish it from immune activation or malignancy within the donor organ.

Adult↗
PubMed1995

Principles of renal replacement therapy in children.

Much has changed in pediatric renal replacement therapy during the past decade. Even the smallest critically ill patients can be temporarily supported, and chronic peritoneal and hemodialysis in young children has become routine. Although improved technical capabilities often may raise difficult ethical dilemmas, the health care team must know that such therapeutic modalities are available for the pediatric patient.

Adolescent↗
PubMed1993

Kidney transplantation in children.

Over the past decade, the success rate of pediatric kidney transplantation has dramatically increased, based on improvements in histocompatibility testing, immunosuppressive management, and diagnosis and treatment of rejection. The 1-year graft survival rate now approaches 90%. The optimal age for recipients as well as for donor organs is greater than six years. Recurrence of primary disease in the graft accounts for approximately 5% graft loss in children. Sequential immunosuppressive protocols have been particularly successful in children, and maintenance immunosuppression routinely includes corticosteroids, azathioprine, and cyclosporin A. Posttransplantation complications include rejection, infection, hypertension, growth retardation, and noncompliance.

Adolescent↗
PubMed1992

Age and the immune response in pediatric renal transplantation.

Because renal transplant outcome is poorer in young children when compared with older children or adults, it is reasonable to question whether immune reactivity relative to renal allograft rejection differs between young children and adults. While this hypothesis is far from established, preliminary data suggest that young children may represent an immunologically-defined subgroup distinct from adults and perhaps at high risk for renal allograft rejection. From a histocompatibility standpoint, infants may show some subtle differences in HLA typing results when compared with older children or adults. Children may also be at higher risk than adults for rejection when the transplant is performed in the presence of a historically positive, currently-negative lymphocytotoxicity crossmatch. Several non-specific tests of cellular immunity have been used to characterize the strong immunologic responder, i.e. the person who has an increase tendency to vigorously reject a renal allograft. Children in general and young children in particular may fall into this group. Children 5 years old and younger have significantly increased numbers of CD2+, CD3+, and CD4+ T lymphocytes when compared with older children. Young children also have higher than expected functional indices of cellular immune function. Taken together, these data suggest that children, and particularly young children, may have a heightened immunologic responsiveness, which may in turn represent an increased propensity for allograft rejection. Appropriate modification in immunosuppression may be indicated to optimize renal transplant outcome.

Adolescent↗
PubMed1992

Acquired cystic disease in chronically rejected renal transplants.

Acquired cystic disease has been documented to complicate most forms of chronic renal damage; it has only infrequently been described in transplanted kidneys. Five patients with noncystic ESRD and chronically rejected transplants in which acquired cystic disease arose are reported. The diagnosis of acquired cystic disease was established in examination of transplant nephrectomies from four patients and a core biopsy from the fifth. The allografts were in place from 44 to 80 months; three patients were treated with hemodialysis before the diagnosis of acquired cystic disease, whereas two received peritoneal dialysis. Three of the four patients evaluated had cysts in the native kidneys. Although papillary hyperplasia of lining epithelium was evident in four specimens, only one kidney was the site of neoplasms in the form of multiple small tubular adenomas. No malignant neoplasms were noted in this study or in the few similar previous ones; however, it is possible that chronically rejected transplanted kidneys may harbor neoplasms with the same malignant potential as those in acquired cystic disease in native kidneys.

Adult↗
PubMed1991

Improved cadaveric renal transplant outcome in children.

We analyzed the results of 165 pediatric cadaver renal transplants performed at the University of California at Los Angeles to identify the factors which are linked to improved allograft survival. Both univariate life-table analysis and the Cox proportional hazard model were used. The use of a sequential immunosuppressive regimen (P less than 0.001) and kidneys from donors of more than 6 years of age (P less than 0.001) were found to be the factors having the most influence on primary graft survival. The sequential regimen was the only factor favorably influencing retransplants. With sequential therapy 1- and 2-year actuarial graft survival rates were 94% and 91% in primary transplants, and 82% and 70% in retransplants. Medication noncompliance exerted a large negative effect on transplant outcome. Of 70 recipients who had been on cyclosporine for at least 6 months, 50% evidenced noncompliance. Sixty-four percent of adolescents were noncompliant. Thirteen percent of the recipients lost their graft because of noncompliance. We conclude that good results can be obtained with cadaver renal transplants in children with a sequential immunosuppressive regimen and the use of kidneys from adolescent and adult donors. Noncompliance is a great barrier to long-term success in pediatric transplantation.

Adolescent↗
PubMed1991

Recombinant human growth hormone treatment of children following renal transplantation.

Nine growth-retarded renal allograft recipients received either thrice weekly or daily subcutaneous recombinant human growth hormone (rhGH) for 6-30 months. The annualized growth velocity for the initial year of rhGH treatment was significantly greater than that of the preceding year (2.5 +/- 2.1 vs 5.7 +/- 2.7; P less than 0.0001). There was no advancement in bone age greater than the increase in chronological age, no significant increase in the mean fasting serum glucose or insulin levels, nor significant decrease in the calculated creatinine clearance following rhGH treatment. However, two patients experienced rejection episodes following rhGH treatment indicating the potential adverse consequences of the treatment on allograft function. This will require further delineation in prospective controlled studies. The serum insulin-like growth factor-1 levels significantly increased at 6 months (P less than 0.009) and 12 months (P less than 0.002) following rhGH treatment compared with baseline values. These preliminary data indicate that rhGH treatment may be effective in improving the growth velocity of growth-retarded renal allograft recipients.

Adolescent↗
PubMed1991

Sensitized B lymphocytes contribute to acute allograft rejection.

The contribution of sensitized B lymphocytes to second-set allograft rejection has been relatively ignored despite their regular appearance in rejecting allografts. This study presents evidence that adoptively transferred sensitized B lymphocytes accelerate the rate of acute allograft rejection in a sublethally irradiated rat cardiac allograft model. Donors of reconstituting B lymphocytes were sensitized with three consecutive ACI skin grafts. Transplantation of a heart from an ACI strain donor into a Lewis strain recipient (complete RT1 mismatch) results in rejection in 6.8 +/- 0.3 days. When the allograft donor and recipient are irradiated with 650 cGy prior to transplantation, rejection occurs at 31.5 +/- 3.0 days. Irradiated recipients reconstituted with 10(6) syngeneic sensitized splenic B cells reject their grafts in 20.1 +/- 2.0 days, while reconstitution with 10(6) unsensitized syngeneic B cells has no effect on the rate of rejection (P = 0.0007). These data strongly suggest that sensitized B lymphocytes have a marked accelerating effect on the tempo of allograft rejection.

Animals↗
PubMed1991

The impact of recombinant human erythropoietin therapy on renal transplantation.

This report describes the potential and actual effects that recombinant human erythropoietin (rHuEpo) may have on the practice of renal transplantation. Three aspects are highlighted. The first is the effects in the dialysis patient transplanted after treatment with rHuEpo. These include the potential risks of graft thrombosis and prolonged initial nonfunction (for which there is little supportive evidence), and the impact on pretransplant immune-modulating regimens, which take advantage of the so-called transfusion effect. As the importance of this effect to overall graft survival has diminished strikingly, this may be of little consequence. The second aspect relates to the highly presensitized dialysis patient. The literature and our own data are presented, showing the beneficial effects of rHuEpo therapy on reducing the level of humoral anti-HLA sensitization. This may lead to benefits that include reduced time on the waiting list for a cadaveric renal transplant, and possibly improved allograft survival. Finally, our data on the use of rHuEpo in 13 patients with anemia (usually due to chronic graft failure) after transplantation is discussed. rHuEpo therapy was effective in all patients, leading to reversal of anemia. Side effects, including hypertension and hypertensive seizures, occurred in the subgroup of patients with significant renal dysfunction (serum creatinine greater than 2.5 mg/DL).

Adolescent↗