Pediatric Renal Allograft Research Articles

INCREASED INTRAGRAFT ANGIOTENSINOGEN GENE EXPRESSION IN POST-TRANSPLANT RECURRENT FSGS

3 We have initiated studies to test the hypothesis that altered intra-renal NFκB regulation and increased expression of NFκB-regulated proteins such as IL-8 and angiotensinogen are involved in the pathogenesis of post-transplant recurrent FSGS. IκBα binds to NFκB, preventing this nuclear factor from upregulating the expression of proinflammatory proteins. Steroids enhance IκBα gene expression. Altered NFκB regulation could result in increased expression of NFκB-regulated factors, allowing pathological processes to be resistant to steroid therapy. We used reverse transcription-assisted competitive PCR to quantify the magnitude of intragraft gene expression of NFκB (p65), IκBα, angiotensinogen, and IL-8 in 65 pediatric renal allograft biopsies including 20 with FSGS and 45 without FSGS. Results are expressed as mean ± s.e. for the quantitative ratio of target gene expression corrected for expression of GAPDH. Our results show elevated intragraft expression of NFκB/IκBα ratio, IL-8, and angiotensinogen in FSGS vs. NON-FSGS, although only angiotensinogen reached statistical significance: TableIn order to perform combined gene analysis, samples were deemed positive for a target gene if the amount of target gene expression was above the 95% upper confidence limit of gene expression for NON-FSGS. Samples positive for 2 or more target genes were separated from samples positive for one or no genes. Of all the FSGS samples, 55% of samples were observed in the group with ≥ 2 genes positive while only 17.8% of NON-FSGS samples were observed in this group (χ2 = 9.274, p<0.005). These preliminary results demonstrate altered expression of NFκB and NFκB-regulated proteins in post-transplant recurrent FSGS. It is likely that altered NFκB regulation accounts for the variable clinical picture of recurrent FSGS post-transplantation. Angiotensin II, the final end-product of angiotensinogen may mediate the steroid-resistant proteinuria and progressive glomerular damage characteristic of this disorder. Further correlation of intragraft IL-8 and angiotensinogen gene expression with clinical status will provide opportunities for innovative therapeutic trials.

Apoptotic cell death in human chronic renal allograft rejection.

Chronic renal allograft rejection is characterized by gradual progression suggesting persistent low-grade injury. Apoptotic cell death may be initiated by low-grade injury secondary to external factors, making apoptosis a potential pathway of chronic rejection. In the present investigation, protocol kidney biopsies of 20 pediatric renal allograft recipients (12 with chronic rejection and 8 with normal histology), 9 pediatric liver allograft recipients, and 7 children with minimal change nephrotic syndrome were evaluated. The presence of apoptotic cell death was studied by determining apoptosis-induced oligonucleosomal DNA fragmentation in the biopsy specimens using 3' end labeling with terminal transferase, gel fractionation, and Southern blotting. The specific cell types with increased DNA fragmentation were determined by in situ 3' end labeling performed on sections of the biopsies. Significant DNA fragmentation was found only in the specimens from patients with chronic rejection. In situ investigation revealed increased apoptosis of both proximal and distal tubular epithelial cells, but not in the glomeruli or interstitium. The mean number of apoptotic tubular epithelial cells per 400x magnified field was higher in the renal allografts than in kidneys of liver transplant recipients or patients with minimal change nephrotic syndrome (2.3 vs. 0.8, P<0.05, in both cases). Our data provide biochemical evidence of increased apoptotic cell death of renal tubular epithelial cells in patients undergoing chronic renal allograft rejection.

Growth hormone treatment of children with chronic renal insufficiency, end-stage renal disease and following renal transplantation--update 1997.

1. Long-term (> 5 years) hGH treatment in children with CRI produces sustained improvement in standardized height. 2. hGH treatment of infants (< 2 1/2 years of age) with CRI is as effective at improving growth velocity as in older children with CRI. 3. Once target height (50th percentile for midparental height) is reached the optimal approach is to pause hGH treatment and observe the patient. If standardized height declines significantly, hGH is effective when re-initiated. 4. Neither short-term nor long-term hGH treatment in children with CRI or in pediatric allograft recipients adversely impacts on carbohydrate tolerance; however, hyperinsulinemia develops which has not been associated with any clinical consequences to date. 5. The presence of renal osteodystrophy may blunt the impact of hGH and predispose to development of slipped capital femoral epiphysis and/or avascular necrosis in children with CRI. Pre-treatment radiologic evaluation and radiologic surveillance with clinical symptoms is indicated. 6. hGH is effective during the initial year of treatment; however the response may be blunted during subsequent years of treatment. The precise mechanism of the latter has not been delineated. 7. hGH has been shown to improve growth velocity in patients undergoing both peritoneal and hemodialysis; however, long-term data are lacking and the response may be less than that achieved in patients with CRI. 8. Growth velocity is uniformly improved in growth retarded pediatric renal allograft recipients receiving hGH. 9. Allograft dysfunction occurs following hGH treatment; however, the relationship to hGH treatment requires delineation. 10. The mechanism responsible for early allograft dysfunction which is usually reversible upon discontinuation of hGH is unknown. 11. Risk factors for the development of an acute rejection episode during the course of hGH treatment are > 1 prior rejection episode and the use of alternate day corticosteroid therapy. 12. The potential exists for an accelerated decline in allograft function following hGH treatment in recipients with chronic rejection. 13. The salutary effect of hGH in this patient population is probably related to increasing the bioavailability of ("free") IGF-I.

Antiepithelial cell antibodies do not impair paediatric renal allograft survival but appear to be associated with acute viral infections

There is a reported association between antiepithelial cell (AEC) antibodies and increased renal allograft loss in paediatric recipients. Our unit experienced a dramatic fall in 1-year graft survival so we undertook a study to determine if AEC antibodies could account for such losses. We also studied healthy children and adults as well as a group of individuals with serologically proven viral infection in an attempt to determine the prevalence and possible aetiology of these antibodies. Sera were screened for AEC antibodies in a microcytotoxicity test using a lung epithelial cell line (A549) as target. The prevalence of these antibodies in our paediatric recipients was similar to that reported elsewhere but we found no correlation between the presence of AEC antibody and allograft loss. Within the control populations, we found the antibody was more prevalent in children than in adults ( p < 0.0001). We also found a strong age banding pattern, with antibody being present in 50% of children under 10 years and declining with increasing age, so that by the age of 16 years the seroprevalence was similar to that found in our adults. However, AEC antibody had a significantly higher prevalence in individual with active viral infection than in our healthy control group ( p = 0.00003). A positive association was noted between rubella and respiratory syncytial virus and AEC antibody presence and a negative association with varicella zoster. We conclude that AEC antibodies do not correlate with increased paediatric renal allograft loss but appear to be linked to certain viral infections.

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.

Triple immunosuppression with subsequent prednisolone withdrawal: 6 years' experience in paediatric renal allograft recipients.

Thirty-four children (< or = 15 years of age) with end-stage renal failure received 39 renal allografts between 1985 and 1991 and were treated with cyclosporin A (CyA), azathioprine and low-dose prednisolone (PNL). We aimed to withdraw PNL by 6 months after transplantation. Median duration of follow-up was 2 years 4 months (range 0.1 month to 6 years 4 months). There were no deaths. Crude graft survival for living-related grafts (n = 9) was 100%, although only 1 patient has been followed for > 2 years. For cadaveric grafts (n = 30), 1- and 5-year actuarial graft survivals were 90% and 79% respectively. At 12 months posttransplant, the median (range) glomerular filtration rate for all patients was 63 (19-109) ml/min per 1.73 m2 (n = 25) and at 5 years was 48 (17-64) ml/min per 1.73 m2 (n = 9). Complications observed included rejection episodes which occurred after discontinuation of PNL. Long-term (after 12 months), 28% of patients remain on PNL. Hypertension was present in more than 50% of patients. Severe CyA nephrotoxicity was not seen. Catch-up growth as determined by the change (delta) in mean height standard deviation score (Ht-SDS) was noted at 1 year [delta SDS/year = +0.60; P < 0.001 (n = 18)] and at 2 years [delta SDS/year = +0.27; P < 0.01 (n = 16)] in pre-pubertal patients. The median Ht-SDS at 2 years for pre-pubertal children was -0.71 SD and growth velocity did not improve thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of HLA matching, type of crossmatch and immunosuppressive therapy on primary pediatric cadaver renal allograft survival

Impact of HLA matching, type of crossmatch and immunosuppressive therapy on primary pediatric cadaver renal allograft survival

Effect of Recipient's Race on Pediatric Renal Allograft Survival: A Single-Center Study

One hundred twenty-seven children (83 males, 44 females, 86 white, 41 nonwhite; mean age 12.1 years) who received 160 renal transplants between 1980 and 1989 were retrospectively studied. Variables such as age, sex, primary diagnosis, type, HLA-DR mismatching, and repeated transplants were compared between races and found not to be significant. However, HLA-A and -B cadaveric-graft mismatching, which was equivalent between whites and nonwhites prior to 1985 (pre-cyclosporine A era), has significantly favored whites (49% with 0 to 2 HLA-A and -B mismatch vs 16% in nonwhites) since 1985 (P less than .05), and a significantly higher proportion of nonwhite patients (59%) were receiving medical assistance (P less than .0001). Graft survival was evaluated with significantly poorer results in nonwhites as compared to whites (P less than .05). Although no difference was found between white and nonwhite cadaveric-graft survival before 1985, nonwhites had significantly worse graft survival since 1985 (72% vs 59% for 1 year and 61% vs 24% for 3 years in whites and nonwhites, respectively; P less than .05). Subpopulations such as nonwhite adolescents, nonwhite females, nonwhites with repeated transplants, and all low socioeconomic patients were identified as high-risk children with poor long-term survival. It is concluded that secondary to poorer matching since 1985 there has been decreased graft survival in nonwhites despite cyclosporine A. Attempts to improve matching and attention to high-risk groups are needed for equivalent survival.

Effects of growth hormone administration in pediatric renal allograft recipients.

The efficacy of recombinant human growth hormone (rGH) was assessed in five pediatric allograft recipients with severe growth retardation despite successful renal transplants. rGH 0.05 mg/kg per dose was given six times weekly by subcutaneous injection to five prepubertal children (mean age 15.2 +/- 2.0 years) all of whom had bone ages less than or equal to 12 years (10.0 +/- 1.4 years), a height standard deviation score of less than -2.5 (-4.9 +/- 1.5), no evidence of catch-up growth, a calculated glomerular filtration rate (GFR) of more than 40 ml/min per 1.73 m2 (51 +/- 6.8 ml/min per 1.73 m2), and stable renal function on alternate-day prednisone (16.7 +/- 2.6 mg/m2 per dose). Growth hormone profiles were abnormal in all children before treatment. rGH administration led to a significant increase in both growth rate (3.5 +/- 1.6 cm/year pre therapy, 8.5 +/- 1.4 cm/year post therapy, P less than 0.001) and percentage of expected growth velocity for bone age (67 +/- 31% pre therapy, 163 +/- 27% post therapy, P less than 0.001) with evidence of true catch-up growth. During the study period, three children had the appearance of secondary sexual characteristics, and one had premature advancement of his bone age. GFR decreased in three children, and in one rGH was discontinued due to a steady rise in serum creatinine. No significant changes were seen in serum calcium, phosphorus, cholesterol, triglycerides, glucose, or thyroid function, although a significant increase in alkaline phosphatase was found. In summary, growth-retarded pediatric renal allograft recipients may have abnormal endogenous GH production and respond favorably to rGH.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant human growth hormone overcomes the growth-suppressive effect of methylprednisolone in uraemic rats

Paediatric renal allograft recipients frequently manifest growth retardation because of suboptimal graft function and/or concomitant corticosteroid treatment. To determine if the growth-suppressive effects of methylprednisolone (MP) could be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH) under conditions of normal and reduced renal function, the following animal model was set up. Female uraemic Sprague-Dawley rats (140 g) together with pair-fed and ad libitum-fed control animals were treated with 6 mg/kg per day MP with or without 10 IU/kg per day rhGH. MP suppressed linear growth and weight gain by 43% and 63%, respectively in ad libitum-fed normal control animals; the suppression was more pronounced in uraemic animals (57% and 107%, respectively). The suppressive effects were independent of food intake. The food conversion ratio (weight gain/food intake) was diminished to one-third in control and to more than one-tenth in uraemic animals. Concomitant treatment with rhGH completely reversed the suppression of length gain and weight gain (total body and muscle) and normalized the food conversion ratio. We concluded that rhGH can completely reverse the catabolic effects of corticosteroids under conditions of normal or reduced renal function. The data provide a reasonable rationale for prospective controlled studies on the use of rhGH treatment in paediatric kidney transplant recipients with growth failure.

Conversion from azathioprine/prednisone to azathioprine/cyclosporin promotes catch‐up growth in pediatric renal allograft recipients

Fifteen pediatric renal allografts recipients under azathioprine (AZA) 2–2.5 mg/kg/day and prednisone (PRED) (5.4 $pM 2.9 mg/m2/d) had their immunosuppression switched to AZA/cyclosporin (CSA) to evaluate benefits on linear growth. Before and after conversion, growth hormone (GH) nocturnal spontaneous secretion (GHss) and somatomedin C basal levels were measured. GH stimulation test (GHst) and SMc generation (SMcG) were also measured but only during the AZA/PRED period. GHst was normal in all children. GH levels increased from 2.6 $pM 2.5 to 20.9 $pM 7.9 ng/ml (p $lt 0.005) after hypoglycemia. The SMc levels, during SMcG, increased from 1.12 $pM 0.41 to 3.73 $pM 1.48 (p $lt 0.005), which is considered a normal response in our laboratory. GH nocturnal secretion inversely correlated to PRED dosage (r = 0.6, p $lt 0.02). GHss increased after PRED withdrawal in the 6 children on PRED 7.0 $pM 3.0 mg/m2/d. On the other hand, bSMc levels did not increase after conversion. After conversion, growth rate increased from 0.34 $pM 0.21 to 0.68 $pM 0.20 cm/month (p $lt 0.0004). The group showed a catch‐up growth from – 3.7 $pM 1.6 to – 2.7 $pM 1.7 standard deviation scores (p $lt 0.0001) after 1 year of follow‐up. Serum creatinine increased slightly from 0.9 $pM 0.2 to 1.0 $pM 0.4 mg/dl. AZA/CSA represents a good alternative for the pediatric recipient of a renal allograft since it is safe to both the child and the graft. This immunosuppressive regimen allows linear growth to occur.

Sonography of complications in pediatric renal allografts.

A total of 420 sonograms of renal transplants in 80 children were obtained because of decreased renal function or to establish a baseline after surgery. We describe normal anatomy of a renal transplant on sonograms, including duplex Doppler and color flow images, and a spectrum of complications. The complications are categorized as follows: parenchymal (drug toxicity rejection, acute tubular necrosis, infection), vascular (pseudoaneurysm, arteriovenous fistula, renal artery stenosis and occlusion), obstructive uropathy, and postoperative fluid collections.

FOLLOW-UP OF CYCLOSPORINE-TREATED PEDIATRIC RENAL ALLOGRAFT RECIPIENTS AFTER CESSATION OF PREDNISONE

We attempted cessation of prednisone therapy in 16 pediatric renal allograft recipients who were between the ages of 3 1/2 and 16 years at the time of transplantation. Fourteen had primary grafts and 2 had second grafts. Nine had cadaver and 7 had living-related donor grafts. At the time of cessation of prednisone, cyclosporine was the only other immunosuppressive therapy for 15 of the patients and 1 patient was receiving CsA and azathioprine. All the patients had stable serum creatinines at the time prednisone was stopped, between 7 months and 5 years posttransplantation. Seven patients have had no episodes of rejection, continuing to receive CsA as their only immunosuppressive therapy and have stable renal function between 16 months and 3 1/2 years (mean: 2 years) after stopping prednisone. Stopping the small maintenance dose of prednisone resulted in improved growth in patients whose epiphyses were not fused. They improved their weight:height ratios and lost their cushingoid appearance. Serum cholesterol levels declined significantly. Patients who required antihypertensive drugs to control their blood pressure while receiving prednisone required fewer or no drugs when off prednisone. Nine patients had acute rejection episodes and were put back on maintenance prednisone following a 3-day steroid pulse. All these patients had a prompt improvement in renal function following the steroid pulse. However, only 3 stabilized function at preprotocol baseline Scr. Four currently have functioning grafts with Scr greater than the preprotocol Scr. Two patients have returned to dialysis. Although stopping steroids is a worthy goal in pediatric renal allograft recipients, we cannot recommend this strategy as routine management because of the 56% rate of acute rejection episodes in the patients who had prednisone withdrawn.

OKT3 Monoclonal Antibody in Pediatric Kidney Transplant Recipients With Recurrent and Resistant Allograft Rejection

Twelve pediatric patients, aged 28 months to 17 years, received OKT3 to reverse renal allograft rejection. In 11 patients, the rejection crisis was resistant to conventional antirejection therapy with high doses of prednisone or polyclonal antithymocyte globulin. Reversal of rejection was successful in 10 patients who completed a treatment course. Because of recurring resistant rejection, five patients received a second course of OKT3, which was successful in reversing the rejection crisis in two. Among these patients, the persistence or the appearance of high levels of circulating T3 lymphocytes after initiating the second treatment course correlated with treatment failure. The immediate side effects associated with OKT3 therapy were translent and medically manageable. We conclude that this monoclonal antibody preparation is a safe and effective treatment for pediatric renal allograft in recipients experiencing rejection crisis resistant to conventional therapy. However, the potential impact of this immunosuppressive medication on long-term renal allograft survival in this patient population remains to be determined.

Growth and Sexual Maturation in Children After Kidney Transplantation

Linear growth and sexual maturation were assessed in 68 long-term pediatric renal allograft recipients (43 boys) receiving dally or alternate-day prednisone therapy. Growth was analyzed both during the prepubertal period and during pubertly. Height at transplantation was >2 SD below the mean in 34.2% of prepubertal children. After the first posttransplant year, 59.2% of the prepubertal children had a normal height increment (>4.8 cm/yr). Onset of pubertly was recorded at a chronologic age of 14.6±1.9 years in boys and 13.3±1.9 years In grils. Height at onset of puberty related to chronologic age was −2.4±1.3 SD. Height velocity during puberty was within normal limits in 62.5% of the children. No significant difference in pubertal growth was detected in patients who had received transplants before and after the onset of puberty. Duration of pubertal development was within normal limits. In grils,menarche was achieved at a mean chronologic age of 15.9 years and bone age 12.9 years. Adult height was attained at an average age of 20.3 years in boys and 18.7 years in girls. Overall, one third of the children attained anadult height >2 SD below the mean. Our data indicate that although poor growth before kidney transplantation has a great inffuence on adult height, the loss of growth potential during pubertal development seems even more important.

OKT3 monoclonal antibody in pediatric kidney transplant recipients with recurrent and resistant allograft rejection

Twelve pediatric patients, aged 28 months to 17 years, received OKT3 to reverse renal allograft rejection. In 11 patients, the rejection crisis was resistant to conventional antirejection therapy with high doses of prednisone or polyclonal antithymocyte globulin. Reversal of rejection was successful in 10 patients who completed a treatment course. Because of recurring resistant rejection, five patients received a second course of OKT3, which was successful in reversing the rejection crisis in two. Among these patients, the persistence or the appearance of high levels of circulating T3 lymphocytes after initiating the second treatment course correlated with treatment failure. The immediate side effects associated with OKT3 therapy were transient and medically manageable. We conclude that this monoclonal antibody preparation is a safe and effective treatment for pediatric renal allograft in recipients experiencing rejection crisis resistant to conventional therapy. However, the potential impact of this immunosuppressive medication on long-term renal allograft survival in this patient population remains to be determined.

Growth and sexual maturation in children after kidney transplantation

Linear growth and sexual maturation were assessed in 68 long-term pediatric renal allograft recipients (43 boys) receiving daily or alternate-day prednisone therapy. Growth was analyzed both during the prepubertal period and during puberty. Height at transplantation was greater than 2 SD below the mean in 34.2% of prepubertal children. After the first posttransplant year, 59.2% of the prepubertal children had a normal height increment (greater than 4.8 cm/yr). Onset of puberty was recorded at a chronologic age of 14.6 +/- 1.9 years in boys and 13.3 +/- 1.9 years in girls. Height at onset of puberty related to chronologic age was -2.4 +/- 1.3 SD. Height velocity during puberty was within normal limits in 62.5% of the children. No significant difference in pubertal growth was detected in patients who had received transplants before and after the onset of puberty. Duration of pubertal development was within normal limits. In girls, menarche was achieved at a mean chronologic age of 15.9 years and bone age 12.9 years. Adult height was attained at an average age of 20.3 years in boys and 18.7 years in girls. Overall, one third of the children attained an adult height greater than 2 SD below the mean. Our data indicate that although poor growth before kidney transplantation has a great influence on adult height, the loss of growth potential during pubertal development seems even more important.

Use of cyclosporine in pediatric renal transplant recipients

Cyclosporine and prednisone were used in combination to produce immunosuppression in 18 pediatric recipients of renal allografts. Ten children received cadaveric kidneys and eight received kidneys from living related donors. With a mean follow-up of 16.5 months (range 7 to 33 months), the patient survival rate is 100% (18 of 18) and the graft survival rate is 83% (15 of 18). Two grafts were lost for nonimmunologic reasons. Currently the group mean (+/- SE) serum creatinine concentration is 1.22 +/- 0.11 mg/dl and creatinine clearance is 69.3 +/- 4.79 ml/min/1.73 m2. Cyclosporine nephrotoxicity has not caused irreversible allograft injury nor led to graft loss in this population. The incidence of treated rejection episodes has been 39% (seven of 18). Only 39% (seven of 18) of children have required hospital readmissions since the initial transplant discharge. There have been no opportunistic infections. In the 15 children with functioning grafts, some linear growth has occurred in 10 of 11 prepubertal and two of four postpubertal patients. Cyclosporine and prednisone have constituted a safe, efficacious immunosuppressive regimen for pediatric renal allograft recipients. Longer follow-up will be necessary to confirm whether these advantages persist beyond 2 years.

The influence of increased renal mass on cardiovascular function in immature dogs.

Pediatric renal allograft recipients receive a relatively greater increase in renal mass than do adult recipients because the donors are usually adults. They also have a higher frequency of posttransplant hypertension and cardiovascular problems. Avoiding other variables common to both pediatric and adult patients including pre-existing hypertension and renal disease and the use of corticosteroids, renal mass was increased by up to 50% in immature dogs by implanting large kidneys from adult dogs. Cardiovascular and renal function were studied before and after transplantation. Blood pressure was decreased in anesthetized mongrel pups at 2 hr and 3 days after surgery by 22 and 6 mm Hg, respectively; pressure was similarly reduced in conscious, chronically catheterized DLA-matched beagle pups maintained for 14 days, from 96.1 +/- 3.0 to 76.8 +/- 6.7 mm Hg (P less than 0.001). Glomerular filtration rate was decreased at 2 hr and 3 days, but was normal at 14 days. Cardiac output was reduced in four of five recipients at 2 hr but was unchanged at 3 days. Plasma volume was increased at 3 days in the mongrel dogs but was normal in the beagles both at 2 and 14 days. We conclude that an increase in renal mass of up to 50% by itself does not cause hypertension in the dog and that other factors may be implicated in pediatric allograft recipients.

CIRCULATING IMMUNE COMPLEXES IN PEDIATRIC RENAL ALLOGRAFT REJECTION

Previous reports on the generation and nephritogenic capacity of post-transplant circulating immune complexes (CICs) are conflicting. To assess the pathogenicity of CICs in acute rejection (AR), 784 CIC determinations were performed on 392 serum samples from 27 pediatric renal allograft recipients using the C1q-solid phase assay (C1q-SPA) and the Raji cell radioimmunoassay (Raji-RIA). Serum samples from transplant recipients not undergoing rejection episodes and from normal subjects served as controls. Of the 784 CIC determinations, 723 (92.3%) were negative in both assays. CICs were present at some point post-transplant in eight (19.6%) recipients. Correlation of CIC levels with allograft rejection was found in only two patients with CIC levels responding to antirejection therapy; however, statistical analysis of data by chi 2 analysis failed to reveal a significant correlation of CICs with AR episodes. Allograft histology in three recipients demonstrated characteristic signs of AR. Immunofluorescent studies did not reveal significant deposition of immunoglobulin or complement. Sucrose density gradient ultracentrifugation studies confirmed the immune complex nature of materials reactive with the CIC assays. There was no immunological evidence supporting antithymocyte globulin (ATG) as an immunogen in patients demonstrating CICs post-transplant. CICs do not appear to be an important mediator of AR. Statistical analysis of data using the chi 2 test failed to reveal a positive correlation of CIC levels with AR or ultimate allograft outcome.