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The success rate of kidney transplantation in young children is higher when the source is a living-related donor (LRD) than when the source is a cadaver. Because the availability of LRD kidneys is not likely to increase, it is important to improve the graft survival of kidneys from cadaveric donors (CD). CD transplants are more likely to fail if the child is under two years, if the organ is stored for longer than 24 hours prior to transplantation and if the child does not have immunosuppression therapy before the operation. Children who are black and those who have previously had a transplant also have an increased risk of graft failure. Using dialysis in children under age two, improving tissue matching and delaying treatment with cyclosporine A may improve CD graft survival.

This report concerns children with nephrotic syndrome (deterioration of kidney function) associated with infection by human immunodeficiency virus (HIV), a topic rarely covered in the medical literature. The authors' pediatric clinic is a referral center for AIDS patients in Brooklyn, New York; between 1984 and 1990, 164 children were treated. Patients were evaluated at the initial visit and examined at least monthly thereafter. In February 1988, patients were enrolled in a research study in which some received albumin and others received immune globulin. Those who developed nephrosis (15 patients) were treated by the renal clinic. By the time of this diagnosis, all patients had clinical signs of AIDS. On average, the patients were diagnosed with AIDS at the age of 3.0 years, and with nephrosis at the age of 4.9 years. Forty-seven of the 164 patients had received either albumin or immune globulin: 8 of these developed nephrosis, a higher incidence than that among patients who did not receive these substances. Histological results from biopsy or autopsy specimens are described. Prednisone was administered to 13 patients without effect on nephrosis. Cyclosporine, an immunosuppressive drug, caused symptom remission, but had to be withdrawn after three months because of possible side effects. Twelve of the 15 patients died prior to this article's publication and another, lost to follow-up, is presumed dead. Three underwent maintenance peritoneal dialysis (in which the peritoneal membrane is used as a filter for toxic substances) to improve the quality of life. This is recommended for children with end-stage renal disease with clinically apparent AIDS. (Consumer Summary produced by Reliance Medical Information, Inc.)

Considerable economic and health-related costs are associated with the life-long maintenance immunosuppressive therapy required to prevent transplant rejection. Generic medications have the potential of providing equivalent therapeutic efficacy at a lower economic cost. In 2001, the American Society of Transplantation invited experts to review the data and issues associated with the approval and use of generic immunosuppressants. A summary of that meeting is reported here.

We have previously documented Caucasian race and cadaver donor source as risk factors for post-transplant lymphoproliferative disorder (PTLD) development in recipients registered in the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). We analyzed data from the Scientific Registry of the United Network of Organ Sharing (UNOS) (from January 1988 to December 1999) to determine risk factors for the development of PTLD in all organ systems and its frequency, and we compared these factors to the risk factors in the most recent NAPRTCS database (1987–2000). In the UNOS database, PTLD was reported in 2365 of 205 114 organ-transplant recipients (1.2%). PTLD was reported in 3% or more of all intestinal and thoracic organ recipients, but in less than 1% of other abdominal organ recipients. Recipient age < 18 years, Caucasian race and male gender were independent risk factors [Odds Ratios (OR) 2.81, 2.22 and 1.40, respectively, p = 0.0001], but not cadaver donor source. The combination of all three risk factors increased the OR to 8.78. The occurrence of PTLD showed a significant rise per year for heart-lung, kidney, kidney-pancreas and liver transplants, but decreased significantly for heart transplants (p < 0.001). Similar frequencies of PTLD were found in smaller organ-specific registries of heart, intestine, pediatric liver and pediatric kidney transplants. The PTLD incidence per year and incidence density have increased in recent years. Young Caucasian males are at highest risk for PTLD development among solid-organ-transplant recipients. The incidence of PTLD is increasing.

Chronic rejection accounted for 32% of all graft losses in 7123 pediatric transplants. In a previous study acute, multiple acute and late acute rejections were risk factors for the development of chronic rejection. We postulated that the recent decrease in acute rejections would translate into a lower risk for chronic rejection among patients with recent transplants. We reviewed our data on patients transplanted from 1995 to 2000, and using multivariate analysis and a proportional hazards model developed risk factors for patients whose grafts had failed due to chronic rejection. A late initial rejection increased the risk of chronic rejection graft failure 3.6-fold (p < 0.001), while a second rejection resulted in further increase of 4.2-fold (p < 0.001). Recipients who received less than 5 mg/kg of cyclosporine at 30 days post-transplant had a relative risk (RR) of 1.9 (p = 0.02). Patients transplanted from 1995 to 2000 had a significantly lower risk (RR = 0.54, p < 0.001) of graft failure from chronic rejection than those who received their transplants earlier (1987–94). Since we were able to demonstrate that there is a decreased risk of chronic rejection graft failure in our study cohort, we would conclude that the goal of future transplants should be to minimize acute rejections.

Historically, higher acute rejection rates, earlier first rejection. and an inability to reverse the rejection characterize pediatric renal transplantation. In recent years, short-term (1-year) graft survival of pediatric renal transplants has steadily improved. To test the hypothesis that these improvements were mediated by changes in acute rejection, we considered the rejection profile of patients who received a renal allograft between 1987 and 1989 (cohort A) and compared it with recipients transplanted between 1997 and 1999 (Cohort B).

Posttransplant lymphoproliferative disorder (PTLD) is an important complication of transplantation. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database has documented 56 cases of PTLD, the largest such series to date.

In an attempt to identify potential markers of steroid-resistance in focal segmental glomerulosclerosis (FSGS) we evaluated intra-graft gene expression of IB, nuclear factor-B (NF-B), and angiotensinogen in 60 biopsies from 27 pediatric renal transplant recipients.Intra-graft NF-B expression was significantly elevated in recurrent FSGS (R-FSGS) (218.3 55.6 ag/fg versus NON-FSGS 121.1 19.9, P0.04) but not in acute rejection. NF-BIB ratios were higher in cadaveric donor versus living related donor recipients (15.7 2.8 vs. 8.8 1.3, respectively, P0.015), and in African-American versus Caucasian recipients (15.6 2.9 vs. 9.1 1.3, respectively, P0.03). Intra-graft angiotensinogen gene expression was significantly elevated in R-FSGS (30.5 8.8 ag/fg R-FSGS vs. 16.0 4.7 NON-FSGS, P0.009). We conclude that increased NF-B and angiotensinogen gene expression are associated with R-FSGS. Increased NF-BIB ratios are associated with cadaveric donor recipients and African-American race.

In children who exhibit a frequently relapsing course of minimal change disease (MCD), treatment is often difficult and frustrating to the physician and the family since the goal of a sustained remission remains elusive. The progression of the disease is often unpredictable from its clinical presentation since the lesion of MCD may evolve into a more severe form, such as mesangial IgM nephropathy or focal segmental glomerulosclerosis (FSGS), without alteration in signs and symptoms. Alkylating agents such as cyclophosphamide, or immunosuppressives such as cyclosporine can induce a more sustained remission, but are fraught with inherent toxicity, which makes difficult the decision to use these drugs in patients with MCD. Over a 10-year period we studied 49 patients who had more than one renal biopsy. Repeat biopsies were performed either to delineate the morphological lesion prior to change in therapy, or to confirm suspected drug toxicity, which would necessitate discontinuation of therapy. A total of 83 repeat biopsies were performed in these 49 patients. Of the 49 patients, 25 had MCD, and in 21 of these the lesion evolved into either IgM nephropathy (n = 7) or FSGS (n = 14). Of patients with IgM nephropathy (n = 12), 50% evolved into FSGS. The clinical diagnosis made prior to the repeat biopsy did not confirm with the histological diagnosis in 43% of cases, and a change in therapy or cessation of therapy was carried out in 43 of 83 repeat biopsy instances. Since the complications were mild and the ability of clinical findings to accurately predict the histological lesion limited, we conclude that repeat renal biopsies are a useful tool to fashion optimal therapy in children with frequently relapsing nephrotic syndrome.

Historically, young children undergoing renal transplantation have lower allograft survival than adults, and potential causes of this are being addressed by the North American Pediatric Renal Transplant Cooperative Study through the National Institutes of Health-sponsored study Cooperative Clinical Trials in Pediatric Transplantation. Included in this study is evaluation of surveillance renal biopsies (SB) and clinically indicated biopsies (CB). Few data exist in children to identify the risk involved with renal transplant biopsies.

Of 2213 primary transplants reported to NAPRTCS between 1/1/87 and 10/31/92, 581 (26.3%) were performed without prior dialysis. The rate of pre‐emptive transplantation (PET) differed by donor source, 35.7% LD and 16.1% CD (p<0.001); gender, 29.6% male and 21.1% female (p<0.001); race, 30.1% white, 16.1% black, 19.5% hispanic, and 20.2% other (p<0.001); recipient age, 0‐1 yr 18.7%, 2‐5 yr 27.9%, 6‐12 yr 30.5%, and 13‐17 yr 22.8% (p<0.001). The graft survival rate was significantly better for both the LD (p<0.01) and CD (p=0.01) grafts in the pre‐emptive group; however, the differences were not significant after adjustment for other variables. The major reasons for pre‐emptive transplantation were the parents' desire to avoid dialysis and the recommendation of the nephrologist/surgeon. The data indicate that preemptive transplantation does not adversely impact on transplant outcome and that the desire to avoid dialysis is the primary motivating factor.

With improved renal graft survival, rehabilitation and growth post‐transplantation are the major challenges to pediatric nephrologists. Recent data from the pediatric renal transplant registry shows that children undergoing renal transplantation have a significant statural height deficit which does not improve in the 1st year after receiving a transplant. Two strategies can be developed to optimize growth post‐transplantation. Using the steroid‐sparing effect of cyclosporine, withdrawal of corticosteroids may be possible in 30‐40% of children, enabling them to grow. Recombinant growth hormone adminstered every other day can be utilized in children who continue to need steroid therapy to improve their growth velocity. This review discusses the mode of action of steroids in inhibiting growth, the methodology of steroid withdrawal post‐transplantation, the measurement of stimulated growth hormone levels, and the use of recombinant growth hormone.

Idiopathic focal segmental glomerulosclerosis is a histologic diagnosis that usually presents as the nephrotic syndrome but, unlike minimal change disease, often leads to renal failure in children. Standard therapies used to treat the proteinuria are often futile, and thus patients are at risk for the multiple complications resulting from persistent, severe proteinuria. Eventually, end-stage renal failure ensues, and the possibility of the disease recurring in the transplanted renal allograft is worrisome. This report reviews the clinical features and outcomes of idiopathic focal segmental glomerulosclerosis in children, the response to newer treatment options, and new insights into understanding what factors may be involved in causing the disorder.

The 1993 North American Pediatric Renal Transplant Cooperative Study annual report summarizes data voluntarily contributed by 82 participating centers on 3,223 pediatric patients who received 2,819 renal transplants from January 1987 through January 1993 and 999 independent courses of dialysis from January 1992 through January 1993. In addition to updating information regarding trends and outcomes in pediatric renal transplantation presented in previous annual reports, 1st-year registry data are presented regarding current practices and trends in chronic dialysis therapy for children and adolescents in North America. Living donor graft (LDG) survival rate was 90% at 1 years 85% at 2 years and 75% at 5 years post transplant. Cadaver graft (CG) survival rates were 76%, 71% and 62% at 1, 2 and 5 years post transplant, respectively. Overall mortality post transplantation continues to be low (CG 6.8%, LDG 4%), mortality remains high in young infants. The dialysis cohort was generally younger than the transplantation cohort. In all age groups, peritoneal dialysis was utilized in the majority of pediatric patients and the overall incidence of peritonitis was 1 episode per 8.2 patient months. External percutaneous catheters were utilized as the predominant chronic hemodialysis access in the study, and access site infections ranged from 6.9% at 1 month to 13.5% at 6 months.

Abstract: With steady improvement in 1- and 5-year patient and graft survivals in the last decade, rehabilitation of the child is the major focus of the transplant physician. The notion that the elimination of the uremic milieu should enable children to grow has not been born out over time, and growth retardation continues to be a serious morbidity in many children despite a well-functioning renal allograft. In children with chronic renal failure prior to renal transplantation, recombinant human growth hormone (rhGH) has been recently shown in controlled trials to improve growth. The use of rhGH in children after renal transplantation is controversial, since uncontrolled studies have questioned its safety. Acute rejection and graft loss have been reported in children after the initiation of rhGH. This study analyzes the data regarding the safety and efficacy of rhGH in children after renal transplantation as presented in seven current published reports. The demographic characteristics of the patients, the dose and duration of rhGH therapy, the “growth” rates of the patients before and after rhGH therapy, renal function before and after rhGH therapy, and other possible complications are reviewed. Based on this analysis, suggestions for future studies are made.

Hypertension is common in children after renal transplantation and is associated with multiple factors. Data regarding the prevalence of post-transplant hypertension and the relationship between immunosuppressive drugs and the presistence of hypertension in a large population of North American children have not been available. This study was designed by the North American Pediatric Renal Transplant Cooperative Study to evaluate in a large diverse multicenter population of children the prevalence of hypertension post transplantation, the type of antihypertensive medication used to treat this hypertension and to determinc the relationship between the blood pressure control and the immunosuppressive therapy. Analysis of 277 patients showed the following: (1) 70% of recipients required antihypertensive medications 1 month post transplant compared with 48% pre transplant; the incidence decreased to 59% at 24 months; (2) the majority of children received multiple drug therpay to control blood pressure; (3) hypertension can be controlled effectively despite inherent etiological factors, such as allograft source, prior hypertension and immunosuppressive therapy.

The North American Pediatric Registry reports that from 1987 to 1989 blacks and Hispanic children accounted for 23% of all renal transplants performed but 38% of those performed for focal segmental glomerulosclerosis (FSGS). From these data, we infer that blacks and Hispanics form a disproportionate number of FSGS patients who progress to end-stage renal disease (ESRD) compared with white children. To explore this hypothesis we assessed our single-center experience of FSGS comparing black and Hispanic with white children. Of 177 black and Hispanic children followed in our clinic for idiopathic nephrotic syndrome (NS) between 1974 and 1989, 57 were diagnosed as having FSGS (group I). The mean age at onset of NS of these group I patients was 7.3±4.6 years and the mean duration of follow-up was 8.25±4.3 years. During the same period, 13 of 65 white patients (group II) with idiopathic NS were found to have FSGS. Their mean age (7.8±4.8 years) and duration of follow-up (8.8±4.8 years) were similar. Therapeutic modalities in the two groups were also similar. Of group I patients, 78% (42/54) reached ESRD compared with 33% (4/12) of group II patients (P<0.01). Life table analysis showed that 50% of black and Hispanic children will reach ESRD within 3 years of FSGS. In a subset of patients, multiple regression analysis revealed that the higher the serum creatinine at the onset of NS (P<0.01,r=0.519), and the higher the serum cholesterol at the onset of NS (P<0.02,r=0.511), the more rapid the progression to ESRD. Based on our findings, a national survey to determine if FSGS is more virulent in black and Hispanic children is warranted.

The North American Pediatric Renal Transplant Cooperative Study collects extensive data on all transplants entered into its registry. For this study we evaluated 568 cadaver kidney and 492 live-donor recipients with graft function at 30 days post transplant. Utilizing maintenance immunosuppressive therapy at 30 days post transplant we evaluated patient and graft outcome, mortality and morbidity over the first 6 months post transplant. For cadaver kidney recipients, 36 patients were receiving prednisone and azathioprine (PA), 114 were maintained on prednisone and cyclosporine (PC) and 418 were on prednisone, cyclosporine and azathioprine (PCA). Patients receiving PA had a greater incidence of rejection prior to 30 days, a greater incidence of hospitalization for rejection and for hypertension over the next 6 months and a greater loss of allograft in the first 6 months compared with the other two groups. The only difference noted between PC and PCA was a lower serum creatinine in the PCA group at 6 months. For living-related kidney recipients, there were 78 patients maintained on PA, 97 on PC and 317 on PCA. Again patients receiving PA had a higher rate of hospitalization for rejection and a higher rate of graft loss. When patients receiving PC were compared with those receiving PCA, no differences were noted in the 6-month serum creatinine values, but a greater percentage of PCA patients were receiving antibiotics on day 30. We conclude that PA is poor therapy for both groups, PCA is ideal therapy for cadaver kidney recipients, but no beneficial effects are noted when PCA is used over PC for live-related donor kidney transplants.

This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1–5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6–12 and 12–17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.

• We studied serum osmolality in 167 consecutive infants admitted for gastroenteritis with 5% or more dehydration. Osmolality was determined by the freezing-point method in a 0.2-mL sample of serum immediately on admission. Forty-one patients (24.6%) had hypo-osmolar dehydration, with a mean osmolality of 257 mOsm/kg (range, 234 to 270 mOsm/kg). Eleven patients (6.5%) had hyperosmolar dehydration, with a mean osmolality of 329 mOsm/kg (range, 312 to 369 mOsm/kg). Simultaneous serum and CSF osmolalities were determined in 14 patients with hypo-osmolar and eight with hyperosmolar dehydration. In patients with hyperosmolar dehydration, serum osmolality correlated well with CSF osmolality, but a poor correlation was seen between serum and CSF sodium levels. Convulsions occurred in two patients in whom the CSF osmolality was greater than the serum osmolality by more than 10 mOsm/kg. Convulsions also occurred in two patients with hypo-osmolar dehydration in whom the CSF osmolality was lower than the serum osmolality by more than 13 mOsm/kg.(Am J Dis Child 1981;135:1000-1005)

• Meningitis and epiglottitis are the clinical manifestations of severe Haemophilus influenzae serotype b infection. Compared with meningitis, epiglottitis occurs in older children. When secondary cases occur within the family, the type of clinical manifestation produced by this serotype is generally similar in siblings. This report concerns the unusual occurrence of meningitis developing in the older child and epiglottitis developing in the younger one. We discuss the possible explanations for this unusual pattern. We also survey the spread of H influenzae both within and outside the family unit and review the present status of histocompatibility antigens and Haemophilus disease.(Am J Dis Child 131:778-781, 1977)

Renal transplantation in children is now a well established mode of optimal therapy for children with end-stage renal disease. The cooperative endeavors of the pediatric renal transplant physicians in the USA and Canada have generated a large volume of data that lends itself to rigorous scientific analysis. With changing practice patterns, the percentage 1− and 2-year graft survivals for cadaveric donor pediatric renal transplants have increased to 83 and 78, respectively, in 1991 compared with 72 and 65 in 1987. Craft failure from acute irreversible rejection continues to take its toll in children under the age of 6 years. With funding from the National Institutes of Health a major cooperative effort has been organized by the North American Pediatric Renal Transplant Cooperative Study to determine the mechanisms that lead to heightened immune response in young children. Surveillance biopsies done in the early post-transplant days will attempt to identify the molecular mediators of acute rejection. Rehabilitation of children will not be satisfactory without accelerated growth after transplantation. Unfortunately, the longitudinal studies of the natural histories of growth after transplantation demonstrates that catch up growth occurs only in a subset of young children and that for the majority of older children, intervention with recombinant growth hormone is necessary. However, concern regarding the potential of recombinant growth hormone to induce chronic rejection necessitates a controlled trial.

For this study, we analyzed the role of rejection in graft failure in children. Rejection results were examined after 3004 pediatric renal transplants 1367 living donor, 1637 cadaver source. A total of 3453 1298 living donor, 2155 cadaver source rejection episodes have occurred, for rejection ratios of .95 for living donor and 1.32 for cadaver source transplants, with a constant difference of 18 points after four months, in the percentage of patients ever experiencing a rejection. Rejection results were examined by patient age 01 vs. 25 vs. 612 vs. ≥13. Rejection ratios, annualized rejection frequency, time to first rejection, and mean number of rejections for patients with rejection were not elevated in the younger patients. However, for the initial rejection episode, recipients less than six years of age had significantly P< .001 poorer outcome from the rejection episode with an increased risk of graft failure in both donor source groups. This age effect on rejection outcome is only seen with the first rejection episode and is not observed with subsequent rejection episodes.

We reviewed the long-term outcome of 25 boys born with posterior urethral valves who were followed longitudinally. Patient age at diagnosis varied from 7 months intrauterine to 7 years postnatal, and the mean duration of followup was 9 years. Of the children 40 per cent had retardation of growth by the end of the followup period and 44 per cent had end stage renal disease. Of the various factors delay in diagnosis and the association of persistent vesicoureteral reflux seem to predict eventual end stage status. In 18 of 25 children the diagnosis of posterior urethral valves was made before they were 2 years old. Only 5 of these children have reached end stage disease status. In comparison, of 7 children whose diagnosis was delayed beyond 2 years 6 have end stage disease (p less than 0.01). Similarly, 7 of 9 children with persistent reflux had end stage disease compared to 4 of 16 who did not have persistent reflux (p less than 0.01). Since end stage renal disease status was reached at widely varying intervals a prolonged followup of children with this anomaly is necessary.

The data base of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) was used to examine the effect of primary diagnosis on the outcome of renal transplantation in children. The relative risk of graft failure for eight diagnostic groups was determined, with patients with congenital and structural anomalies of the urinary tract serving as the reference group. Covariate analysis was used to control for the effects of age, race and transfusion history in recipients of living-related donor kidneys, and for age, donor age, antilymphocyte prophylaxis, prior transplantation, prior dialysis and cold ischemia time in recipients of cadaver kidneys. In recipients of living-related donor kidneys, the lowest graft failure rates were associated with the diagnoses of cystinosis, familial nephritis and hemolytic uremic syndrome (HUS), while the highest failure rates were observed in patients with a primary diagnosis of congenital nephrotic syndrome (CNS) or focal segmental glomerulosclerosis (FSGS). In cadaver allograft recipients, the lowest graft failure rates were associated with primary diagnoses of glomerulonephritis, congenital/structural disease and cystinosis, while patients with FSGS, HUS and CNS had the highest graft failure rates. This study suggests that patients with a primary diagnosis of cystinosis have superior outcomes, while the diagnoses of FSGS and CNS carry with them the highest risks of graft failure.

From January 1987 to January 1992 the North American pediatric Renal Transplant Cooperative Study registered and followed 2,037 children and adolescents 17 years of age or less who received 2, 197 renal transplants at 75 participating centers in the United States and Canada. The cumulative experience over 5 years of data collection demonstrated trends in renal transplantation practice for pediatric patients. The percentage of live donor organ recipients receiving donor-specific blood transfusions decreased from 40% in 1987 to less than 12% in 1991; random blood transfusions also were used less frequently during the most recent 2 years of the study. Immunosuppressive therapy on posttransplant day 0 or 1 with polyclonal and monoclonal antilymphocyte agents was used in over 40% of transplants. There was also a notable preference for the combined use of prednisone, azathioprine and cyclosporine as maintenance immunosuppression. The percentage of live donor source graft recipients receiving cyclosporine increased from 78% in 1987 to 90% in the most recent year, and considered together, nearly 90% of live donor and cadaver organ recipients received cyclosporine. The observed graft survival probabilities for live donor grafts were 88%, 83%, 81% and 76% at years 1–4 post transplantation, respectively. The 1st through 4th year graft survival probabilities for cadaver grafts were 74%, 68%, 63% and 58%, respectively. The five most common causes of pediatric end-stage renal disease have remained as: hypoplastic-dysplastic kidney, obstructive uropathy, focal segmental glomerulosclerosis, reflux nephropathy and systemic immunological diseases throughout the 5 years of this study. There has been a decrease in children 2 years of age or less undergoing transplant surgery. On average, 50% of graft failures were due to the various forms of rejection. Vascular thrombosis (14%) and recurrence of primary renal disease (7%) were the next most frequently encountered causes of graft failure. Poor linear growth was identified as a problem affecting the majority of children both before and after transplantation. Post transplant linear growth was best among recipients less than 6 years of age at transplantation and recipients of all ages who received alternate-day prednisone. A total of 16 malignancies were reported during the 5 years of study. A total of 105 deaths were reported, with infection (41%) the most common primary cause of death. The 2-year patient survival probabilities were 95.5% and 93% for recipients of live donor and cadaver grafts, respectively.

Steroid therapy posttransplantation has been correlated with hyperlipidemia and hypertension. With improved graft survivals in the cyclosporine (CsA) era, post-tx hyperlipidemia and hypertension may place children at high risk for early atherosclerosis. Presently there are no large studies assessing the metabolic effects of steroid withdrawal in tx children. Thus, we report on the effect of prednisone withdrawal on blood pressure, weight, and serum lipid levels in children post-tx maintained on CsA alone. Pred taper is attempted in patients on CsA (6–7 mg/kg/day) with stable graft function and is extended over a 6-month period. Once a rejection is diagnosed pred is restarted and no future attempts to withdraw are made. BP, weight, and overnight fasting serum cholesterol (Schol) levels were measured 1 month prior to complete withdrawal (A), and after 6 months without pred (B). In patients requiring the restart of pred, subsequent measurements were obtained 6 months later (C). Of 74 tx children, 7 had primary nonfunction. Pred was successfully withdrawn in 49 (33) of the remaining 67. Of these patients, 42 (14/33) are still maintained off pred with stable renal function for a mean duration of 58.5 months (range 8–99 months). Nineteen patients had to be restarted on pred secondary to rejection between 7–36 months after withdrawal. Three of the patients subsequently lost their grafts to

Steroid-resistant FSGS and its recurrence posttrans-plantation are predominantly seen in children. We report on the largest pediatric transplant population for FSGS with similar numbers of azathioprine- and cyclo-sporine-treated patients analyzed for recurrence. Of 70 patients with idiopathic FSGS identified over the years 1974–1989, 49 progressed to end-stage renal disease and 28 received 42 transplants (17 live-related donors, 25 cadaveric). Seventeen patients each received one transplant, 9 patients each received two transplants, and one patient each received three and four transplants. The mean age at diagnosis of FSGS was 9.1±4.2 years, the mean duration of FSGS prior to reaching ESRD was 2.2±1.3 years, and the mean duration on dialysis prior to transplantation was 9.7±6.3 months. Primary nonfunction was observed in 2 transplants; in the remaining 40 transplants, 6 recurrences were noted (15). Recurrences were noted in four AZA and prednisone (n=22) and two CsA and prednisone (n=18) recipients. Risk factors analyzed for recurrence included race, age at FSGS, histological and clinical severity of FSGS, classification of FSGS, duration of disease, interval on dialysis, multiple transplants, and HLA matching. Only age at onset of FSGS was predictive of recurrence. The incidence of recurrence was higher in children ±6 years of age compared with those over 6 years (P.05). All 4 patients receiving AZA and prednisone went on to lose their grafts due to recurrence. Recurrent proteinuria in the 2 CsA and prednisone recipients was controlled by gradually increasing the CsA dose from 15 mg/kg/day to 27 and 35 mg/kg/day. Remission of the nephrotic syndrome was induced within 60 days in both patients. Presently, both grafts are functioning 24 and 16 months posttransplant with serum creatinines of 0.9 and 0.5 mg/dl, respectively. We conclude that recurrence is predominantly seen in very young children and occurs even under CsA immunosuppression. High-dose CsA may control the recurrent proteinuria

Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the incidence and possible causes of graft thrombosis in pediatric renal transplant recipients. Between January 1987, and November 1989, 1045 renal transplants in recipients 18 years of age were registered in the study, including 484 living-related donor and 561 cadaver donor transplants. There were 213 graft failures (67 LRD, 146 CAD), and of these 27 were caused by thrombosis (8 LRD, 19 CAD). Thrombosis occurred in 2.6 of all transplants and accounted for 22.5 (27/120) of all graft failures that occurred in the first 60 days following transplantation.

A worldwide shortage of cadaveric donors has led to the increased utilization of elderly living donors, with controversial results. In an attempt to assess the effect of donor age on graft survival and subsequent renal function, we analyzed our clinical results in 276 consecutive recipients of living related renal transplants spanning both the cyclosporine and the azathioprine eras, of whom a total of 44 recipients received kidneys from donors over 55 years old. All recipients were otherwise similar in age, race, haplotype mismatch, number of retransplants, and number of pretransplant transfusions, apart from an increased number of diabetics among the CsA-treated recipients of elderly kidneys (38 vs. 14). The cumulative patient and graft survival rates at 1 and 5 years were independent of donor age whether CsA or AZA was utilized. Nor was the incidence of rejection or infection significantly different in the older donor group when compared with the younger cohort. Short-term and intermediate-term renal function, as assessed by serum creatinine, was however poorer but stable in the older donor group when compared with the younger one. The mean serum creatinine levels at 1 year in the CsA- and AZA-treated recipients of kidneys from older donors were 2.4 and 2.0 mg/dl, respectively, compared with 1.6 and 1.4 mg/dl, respectively, when the donor age was less than 55 years (P<0.001). Since renal function at the end of the first posttransplant year is considered a determinant of long-term graft survival, this is a cause for concern, but in view of the universal shortage of organs and the negligible morbidity to donors, renal transplantation from elderly living donors remains an acceptable practice.

Of 2457 patients in the North American Pediatric Renal Transplant Cooperative Study registry who were followed for 5481 patient-years after the index transplantation, we observed 136 deaths, for an average annual rate of 24.8 deaths per 1000 patient-years. Death resulted primarily from infection (n=55, 40), cardiovascular causes (n=28, 21), hemorrhage (n=16, 12), and malignancies (n=9, 7). Cadaver-donor source was associated with greater mortality (6.7) than a living-donor source (4.0) (P<0.005). Recipients aged 0–1, 2–5, 6–12, and 13–17 years old had mortality rates of 17.5, 8.0, 3.6, and 4.5, respectively (P<.001). Mortality rates increased substantially when examined by recipient and cadaver donor ages (mortality rates of up to 45), the greater the concordance between young donor and recipient ages. Interestingly, acute tubular necrosis and graft failure less than 30 days after transplantation (GH30) were each associated with markedly elevated mortality rates. (The risk ratio for ATN was 3.1 [P<0.001] and for GF30 it was 6.4 [P<0.001].) Mortality after transplantation was also affected by the underlying renal disease, with high mortality rates observed for oxalosis (n=21, 33.3), congenital nephrotic syndrome (n=79, 15.2), pyelo/ interstitial nephritis (n=54, 11.1), and Drash syndrome (n=14, 21.4).

Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the effect of donor age on graft survival for pediatric recipients of cadaver donor renal transplants. Between January 1, 1987, and November 16, 1990, 787 cadaver donor renal transplants in children <18 years of age were registered in the study. The ages of the donors were ≤5 years in 203 transplants, between 6 and 9 years in 87, between 10 and 39 in 389, and ≥40 years in 108.

Abstract: Changes in height deficit and standard deviation score (SDS) were evaluated in 524 recipients who were growth retarded at transplantation (SDS>−2.00) and were followed for at least 2 years post transplant. At 2 years the Δ SDS was 0.32±0.04 and the Δ height deficit was 0.75±0.23. Therefore despite improvement in the SDS at 2 years post transplant, the change in height deficit was <1 cm. Change in height deficit may be a better indication of “catch-up” growth following transplantation.

Noonan’s syndrome is an eponymic designation that has been used during the last 8 years to describe a variable constellation of somatic and visceral congenital anomalies, which includes groups of patients previously referred to as male Turner’s, female pseudo-Turner’s and Bonnevie-Ullrich syndromes. It is now recognized that both sexes may show the stigmas of this condition and, unlike Turner’s syndrome, there is no karyotype abnormality although there is often a familial pattern. The most commonly observed anomalies include webbing of the neck, hypertelorism, a shield-shaped chest and short stature. Congenital heart disease, principally pulmonary stenosis, and sexual infantilism often with cryptorchidism in the male subject are additional associated anomalies in this syndrome.

• We studied the long-term outcome of lupus nephritis in 23 black and Hispanic children. The follow-up period ranged from two to 16.5 years, with a mean follow-up of 5.4 years. The mean age at onset was 10.1 years, which is younger than that described in recent series of children with lupus nephritis. All patients had renal involvement, including four normotensive patients with normal renal function and normal urinary sediment. When children whose disease started before the age of 10 years were compared with patients older at onset, there were no significant differences regarding the type of lesion or duration of therapy, but a higher incidence of renal death (.02&lt;P&lt;.05) was noted in younger children. Overall, 25% of our patients have died of renal causes, and another 25% have been undergoing dialysis, receiving transplants, or in chronic renal failure. The mortality in our series was higher than that reported in other series of children with lupus nephritis in recent years. Age and race may be acting synergistically to produce the higher mortality and morbidity.(Am J Dis Child 1983;137:481-483)

Cyclosporine G (CsG) like cyclosporine A (CsA) is a cyclic endecapeptide where the alpha-amino butyric acid residue in position 2 is replaced by norvaline. We studied the effects of both drugs on renal function in a nontransplant rat model to avoid the additional variable of rejection. Age- and weight-matched pairs of male Sprague-Dawley rats were treated subcugtaneously for 21 days with a daily dose of 25 mg/kg bw of either powdered CsA or CsG dissolved in 1 ml of olive oil. A control group (C) received olive oil only. Blood pressure (BP) and creatinine (Cr) were measured on days 0, 7, 14, and 21. On day 22, animals were weighted, aqnesthetized, and glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured using C14inulin and 3RpareAminohippuric acid, respectively, Renal plasma flow and glomerular filtration rate were unaltered in CsG-treated animals compared to controls but significantly reduced in CsA-treated animals. Histologically, vacuolization and microcalcification were seen in significantly greater frequency among the CsA-treated animals. CsG with lesser nephrotoxic potential may prove to be of use in maintenance of therapy of transplants as well as selected autoimmune disorders.

In Reply.—Dr Sawyer's second patient falls in the category that we prefer to call coprimary rather than secondary. In our review of intrafamily spread of Haemophilus influenzae infection in confirmed cases, the time interval between the disease in the index case and siblings ranged from 24 hours to two months, with a mean time interval being 8.5 days. Our present policy is to diagnose H influenzae meningitis expediently by smear (80% to 85% positive) and counterimmunoelectrophoresis (90% to 95% positive). Once a diagnosis is made, we ask the parents to bring in the siblings. Cultures are taken from all siblings, and those under 3 years of age are given ampicillin, 100 mg/kg/day orally, for ten days. Using this regimen, we have not seen a secondary or coprimary case in two years. Siblings over 3 years of age, if culture positive, are also treated; the rationale here is to reduce