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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
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↗
PubMed1990

Technical factors contributing to successful kidney transplantation in small children.

Cadaveric renal transplantation in small children has not been as successful as either cadaver transplantation in older children, or adults, or living-related transplantation in small children. We report the results of cadaver renal transplantation in 17 children 6 years or younger with only 1 graft lost within 1 year after transplantation. The important technical factors that have enabled these improved results include careful intraoperative fluid management, use of adult kidneys with arterial anastomoses to the common iliac artery or aorta, and sequential immune suppression.

Child↗
PubMed1990

Effects of recombinant human erythropoietin on HLA sensitization and cell mediated immunity.

Highly presensitized patients wait longer for a renal allograft than unsensitized patients and have a poorer allograft survival rate. Repeated blood transfusions have been implicated in the induction and maintenance of sensitization. To determine the effect of recombinant human erythropoietin (rHuEPO) therapy on five transfusion dependent, highly sensitized adolescents on dialysis, we serially measured percentage panel reactive antibody (%PRA) levels, titers of identifiable discrete anti-HLA Class I antibody specificities, and non-specific indices of cellular immunity before and following initiation of rHuEPO therapy. Although four of the five patients had previously rejected at least one renal allograft, the removal of chronic antigenic stimulation from blood transfusions led to a marked reduction in anti-HLA antibody titers to recognizable private and public specificities (P less than 0.001) and a reduction of mean %PRA from 80% to 56% (P less than 0.05). Each patient demonstrated a reduction of two or more dilutions to at least two anti-HLA antibody specificities. A control group of five patients matched for age, transfusion dependence and sensitization status demonstrated no change during a comparable time interval. PHA responsiveness decreased significantly in the rHuEPO group whereas autologous and allogenic mixed lymphocyte response, spontaneous blastogenesis and T-cell subsets did not. These data indicate that in highly sensitized dialysis patients rHuEPO may lead to decreased sensitization, shorter waiting time on dialysis and possibly improved allograft survival rates.

Adolescent↗
PubMed1990

The impairment of true glomerular filtration rate in long-term cyclosporine-treated pediatric allograft recipients.

We performed indium-111-DTPA plasma clearance studies in 61 pediatric kidney and liver recipients treated with cyclosporine to compare true glomerular filtration rate with calculated GFR (cGFR). The mean true GFR of 61.9 +/- 36.6 ml/min/1.73 m2 indicated renal impairment. The mean cGFR of 85.2 +/- 22.4 ml/min/1.73 m2 was significantly higher (P less than 0.001), and overestimated GFR by 38%. cGFR alone did not accurately reflect the degree of renal dysfunction. A group of 48 pediatric orthotopic liver transplant recipients was studied in more detail: 73% of these patients had a true GFR less than 70 ml/min/1.73 m2, while 85% had a true GFR below 90 ml/min/1.73 m2, the lower limit for normal GFR in children. The mean true GFR for patients treated more than 24 months with CsA was lower (P = 0.02) than patients treated with CsA for 12 to 24 months. OLT patients with normal true GFR (greater than 90 ml/min/1.73 m2) had significantly lower plasma CsA levels, and 50% of patients with a true GFR less than or equal to 50 ml/min/1.73 m2 had hypertension. There was no effect on true GFR of age, liver function, azathioprine use, or peritransplant treatment with other nephrotoxic drugs. We conclude that true GFR is significantly impaired in long-term CsA-treated allograft pediatric recipients. Calculations of GFR underestimate the degree of renal dysfunction. As patients treated greater than 24 months had the lowest true GFRs, the fall in GFR may be progressive.

Adolescent↗
PubMed1990

The effect of hypoprolactinemia alone and in combination with cyclosporine on allograft rejection.

Recent evidence suggests that prolactin has a role in regulating immune function. Hypophysectomy or administration of bromocriptine results in suppression of the immune response, which is reversed by the administration of prolactin. Hypoprolactinemia has been shown to augment the immunosuppressive effect of cyclosporine. We studied the effect of hypoprolactinemia induced by a new drug, CQP 201-403, on the survival of heterotopic cardiac allografts in the rat and the ability of peripheral blood lymphocytes to respond in vitro to plant mitogens. CQP treatment alone produced a small increase in graft survival but no change in lymphocyte in vitro proliferation (P less than 0.05). CQP treatment greatly enhanced the immunosuppressive effect of cyclosporine on graft rejection and in vitro lymphocyte function (P less than 0.02). We conclude that modulation of prolactin may be a useful adjunct to cyclosporine immunosuppression.

Animals↗