Short-term pediatric renal transplant survival: blood pressure and allograft function.

Hypertension is prevalent after renal transplantation (Tx) and associated with graft failure in children and adults. However, the effect of blood pressure (BP) on short-term renal allograft function is uncertain. We assessed the associations among BP pretransplant, and 3 months and 1 yr post-transplant, and 1-yr post-transplant measured glomerular filtration rate (mGFR) in 61 children with a functioning graft. The GFR was determined using a single intravenous (i.v.) injection of Optiray 350(R). Data were collected between January 1994 and January 2000. The mean mGFR 1 yr after renal transplant was 63.6 +/- 19.9 mL/min/1.73 m2 in 26 live donor recipients and 50.8 +/- 23.3 mL/min/1.73 m2 in 35 cadaveric donors (p = 0.029). Correlation analysis showed significant negative associations of 1-yr mGFR with systolic blood pressure (SBP) and diastolic blood pressure (DBP) 3 months after renal Tx (r = - 0.58, p < 0.0001 and r = - 0.50, p < 0.0001, respectively), and with SBP (r = - 0.37, p = 0.003) and DBP (r = - 0.32, p = 0.01) 1 yr after renal Tx. Multi-variate regression analysis showed that the SBP 3 months after Tx (p < 0.001), number of acute rejections (p = 0.002), donor age (p = 0.02), and cold ischemia time (p = 0.03) were independent predictors for the 1-yr mGFR. These results indicate that a higher SBP in the first few months post-renal Tx is associated with decreased renal allograft function in children 1 yr post-Tx.

Factors influencing short-term and long-term pediatric renal transplant survival.

OBJECTIVE: To determine the patient and donor characteristics important for short-term and long-term renal transplant survival at Cincinnati Children's Hospital Medical Center. METHODS: Cumulative transplant survival was calculated and univariate analysis of graft survival performed on 206 transplants done since 1970 in 148 pediatric patients. Grafts to black recipients were analyzed separately. Short-term graft survival is defined as 1-year allograft survival and long-term graft survival as graft half-life (t1/2) survival for allografts functioning after the first posttransplant year. RESULTS: One-year graft survival of living-related donor (LRD) and cadaver donor (CAD) transplants was 77% and 62%, respectively. Graft t1/2 was 11.2 years for LRD and 9.8 years for CAD grafts. The CAD 1-year graft survival when the recipient or donor was younger than 7 years was 36% and 41%, respectively. The LRD 1-year graft survival to children younger than 7 years was 88% versus 75% in older children. Graft survival at 1 year was similar for CAD primary and retransplants (60% vs 65%), but graft t1/2 better for CAD primary grafts (17.8 years vs 5.0 years, P < 0.001). Preemptive LRD grafts performed similarity at 1 year and better over the long term compared with patients who had long-term dialysis (85% vs 74%, P = NS; and 16.9 years vs 8.0 years, p < 0.001). Preemptive CAD grafts did poorly, with 1-year graft survival of 38%. Administration of Cyclosporine A (CsA) improved CAD 1-year graft survival (76% vs 54%, p < 0.001) but not long-term survival. Thirty grafts to 24 black children had a 1-year survival of 48%, with no graft surviving more than 5 years. CONCLUSIONS: Living-related donor transplantation should be aggressively pursued for young children. If a LRD is unavailable and the young child's medical condition is stable, delay in CAD transplantation should be considered, with dialysis before transplant. Use of CsA improves 1-year pediatric graft survival, but does not improve graft survival after 1 year at the Children's Hospital Medical Center. New strategies to improve graft survival in black children should be pursued.

Autosomal dominant hypophosphatemic rickets/osteomalacia: clinical characterization of a novel renal phosphate-wasting disorder.

Renal phosphate-wasting disorders are the most common form of hereditary rickets and osteomalacia in western countries. Although autosomal dominant transmission of renal phosphate wasting has been described, previous studies included too few affected individuals to adequately characterize the disorder. We performed clinical and biochemical evaluations of individuals from a large kindred with autosomal dominant hypophosphatemic rickets/osteomalacia. We identified 23 affected members in this family, and for some individuals, follow-up was up to 25 yr. As patients were all members of the same kindred, we had the opportunity to determine the clinical manifestations of the disorder in patients who presumably all have the same genetic mutation. Affected individuals have isolated renal phosphate wasting and inappropriately normal serum calcitriol concentrations. The inheritance pattern was consistent with autosomal dominant transmission with variable penetrance. The family contained two subgroups of affected individuals. Group 1 consisted of patients who presented with renal phosphate wasting as adolescents or adults. These patients presented with bone pain, weakness, and insufficiency fractures, but did not manifest lower extremity deformity. Group 2 consisted of patients who presented with phosphate wasting, rickets, and lower extremity deformity as children. Surprisingly, some individuals in group 2 lost the renal phosphate-wasting defect after puberty. In conclusion, autosomal dominant hypophosphatemic rickets/osteomalacia is an inherited disorder of isolated renal phosphate wasting. The spectrum of disease includes delayed onset of penetrance and loss of the renal phosphate-wasting defect. Our results have implications in the evaluation of patients who present with renal phosphate wasting as either adults or children.

Autosomal dominant hypophosphatemic rickets is linked to chromosome 12p13.

Autosomal dominant hypophosphatemic rickets (ADHR) is an inherited disorder of isolated renal phosphate wasting, the pathogenesis of which is unknown. We performed a genome-wide linkage study in a large kindred to determine the chromosome location of the ADHR gene. Two-point LOD scores indicate that the gene is linked to the markers D12S314 [Z(theta) = 3.15 at theta = 0.0], vWf [Z(theta) = 5.32 at theta = 0.0], and CD4 [Z(theta) = 3.53 at theta = 0.0]. Moreover, multilocus analysis indicates that the ADHR gene locus is located on chromosome 12p13 in the 18-cM interval between the flanking markers D12S100 and D12S397. These data are the first to establish a chromosomal location for the ADHR locus and to provide a framework map to further localize the gene. Such studies will permit ultimate identification of the ADHR gene and provide further insight into phosphate homeostasis.

Renal allograft survival according to primary diagnosis: a report of the North American Pediatric Renal Transplant Cooperative Study.

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.

A prospective, double-blind study of growth failure in children with chronic renal insufficiency and the effectiveness of treatment with calcitriol versus dihydrotachysterol. The Growth Failure in Children with Renal Diseases Investigators.

Because controlled trials in adults have shown accelerated deterioration of renal function in a small number of patients receiving calcitriol for renal osteodystrophy, we initiated a prospective, randomized, double-blind study of the use of calcitriol versus dihydrotachysterol in children with chronic renal insufficiency. We studied children aged 1 1/2 through 10 years, with a calculated glomerular filtration rate between 20 and 75 ml/min per 1.73 m2, and with elevated serum parathyroid hormone concentrations. Ninety-four patients completed a mean of 8.0 months of control observations and were randomly assigned to a treatment period; 82 completed the treatment period of at least 6 months while receiving a calcitriol dosage (mean +/- SD) of 17.1 +/- 5.9 ng/kg per day or a dihydrotachysterol dosage of 13.8 +/- 3.3 micrograms/kg per day. With treatment the height z scores for both calcitriol- and dihydrotachysterol-treated groups showed no differences between the two groups. In relation to cumulative dose, there was a significant decrease in glomerular filtration rate for both calcitriol and dihydrotachysterol; for calcitriol the rate of decline was significantly steeper (p = 0.0026). The treatment groups did not differ significantly with respect to the incidence of hypercalcemia (serum calcium concentration > 2.7 mmol/L (> 11 mg/dl)). We conclude that careful follow-up of renal function is mandatory during the use of either calcitriol or dihydrotachysterol because both agents were associated with significant declines in renal function. There was no significant difference between calcitriol and dihydrotachysterol in promoting linear growth or causing hypercalcemia in children with chronic renal insufficiency. Dihydrotachysterol, the less costly agent, can be used with equal efficacy.

Renal transplantation in children and adolescents: the 1992 annual report of the North American Pediatric Renal Transplant Cooperative Study.

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.

Does human lymphocyte antigen matching improve the outcome in pediatric renal transplants?

Adult studies have shown a high renal graft survival if the donor and recipient match for each antigen of the human lymphocyte antigen (HLA)-A, B and DR loci (six-antigen match). The 4 yr of data from the North American Pediatric Renal Transplant Cooperative Study Registry show a statistically beneficial effect of DR matching for cadaver graft outcome. No antigen matching clearly has a worse outcome, 72% at 1 yr versus those with one or more antigen matching at each loci with a 1-yr graft survival of 81% and 2-yr graft survival of 69%. The long-term improved outcome from better antigen matching suggests that cadaver donor allograft organ assignment should address both the need of the center-driven and patient-driven concepts of recipient selection to achieve the best use of this scarce resource and an improved quality of life.

Renal transplantation in children. A report of the North American Pediatric Renal Transplant Cooperative Study.

BACKGROUND: Previous studies of renal transplantation in children have focused on the survival of grafts and patients. Little information is available about the cause of renal disease, the sources of donated organs, or children's growth after transplantation. The North American Pediatric Renal Transplant Cooperative Study was organized to identify the diseases that require transplantation and to analyze factors that affect the success of transplantation in children. METHODS: We collected data from 73 pediatric transplantation centers from 1987 through 1990. These data included information about demographic characteristics of patients, graft function, and therapy one month after transplantation and every six months thereafter for each patient 17 years of age or younger. RESULTS: Altogether, 1550 children received 1667 renal allografts during this period; 31 percent of the children were five years of age or younger. Forty-three percent of the transplanted kidneys came from a living related donor, and 57 percent from a cadaver. The two most common causes of renal disease leading to transplantation were congenital malformations of the kidneys and urinary tract (42 percent of the patients) and focal segmental glomerulosclerosis (12 percent). One year after transplantation, the rate of graft survival in recipients of a kidney from a living related donor was 89 percent; it was 80 percent after three years. For recipients of cadaver kidneys, the comparable rates were 74 percent and 62 percent, respectively (P less than 0.001). The best growth was observed in patients who were no more than five years old at the time of transplantation. During follow-up, 79 patients died, and cancer developed in 12 patients. CONCLUSIONS: The most common causes of end-stage renal disease in children and adolescents are congenital malformations of the kidneys and urinary tract and focal segmental glomerulosclerosis. The rates of graft survival at one and three years are better in children and adolescents who receive a kidney from a living related donor than in those who receive a kidney from a cadaver.

Prolonged reversible renal failure with nephrotic syndrome.

Steroid nonresponsive nephrotic syndrome in a 15-year-old girl with reversible renal failure required dialysis and aggressive nutritional therapy for 1 year. Severe interstitial edema and foot process fusion were the only processes identified to explain the renal failure. Diabetes-like alterations of the glomerular capillary wall basement membrane may have been an outcome of the intense alimentation.

The 1989 report of the North American Pediatric Renal Transplant Cooperative Study.

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.

Membranoproliferative glomerulonephritis: the Cincinnati experience--cumulative renal survival from 1957 to 1989.

Seventy-six children with idiopathic MPGN have been followed at this medical center since 1957 (mean 10.6 years of disease). Seventy-one of the children have been treated with a regimen of prednisone (mean 7.7 years of treatment). Monotherapy with alternate-day prednisone was used in 50 of the children. Other immunosuppressive and cytotoxic drugs have not been used since 1981. In the 71 treated patients, the cumulative renal survival (creatinine less than 3.0 mg/dl (265.5 mumol/L)) was 82% in the tenth year and 56% in the twentieth year after disease onset. Cumulative renal survival, calculated from the date of initiation of the prednisone regimen, was 75% in the tenth year and 59% in the twentieth year. As our experience with this disease has increased, long-term cumulative renal survival has improved.

Linear growth and anthropometric and nutritional measurements in children with mild to moderate renal insufficiency: a report of the Growth Failure in Children with Renal Diseases Study.

During the control period of the Growth Failure in Children With Renal Diseases Study, investigators at 23 centers were able to observe and characterize growth and to make anthropometric and nutritional measurements in 82 children with mild to moderate renal insufficiency. As a multicenter, controlled clinical trial designed to study the relative efficacy of 1,25-dihydroxyvitamin D3 and dihydrotachysterol in the treatment of renal osteodystrophy, no prior vitamin D exposure and a creatinine clearance of 25 to 75 ml/min/1.73 m2 were criteria for entrance into the clinical trial. Ages ranged from 18 months to 11 years (mean 5.6 +/- 3.1 years), and distribution by age category was as follows: 38%, 1 to 3 years; 28%, 4 to 6 years; and 34%, 7 to 10 years. There was a 3:1 male/female ratio; 72% of the patients had congenital disease by the International Classification of Diseases (ninth revision). Mean creatinine clearance was 49.5 +/- 20 ml/min/1.73 m2. The C-terminal parathyroid hormone values (1121 +/- 1562 pg/ml) were well above 2 SD of the mean of a normal growing population of similar age. Parathyroid hormone values correlated with degree of renal insufficiency (r = -0.57) and with height by bone age but not with chronologic height or growth velocity. The bone age/height age ratio, a predictor of growth potential in normal children, was low for the entire series of patients (0.88 +/- 0.35) but failed to correlate with growth velocity and was negatively correlated with rising parathyroid hormone levels. Average values for height, weight, triceps skin fold, mid-arm muscle circumference, and body mass index were within 2 SD of the mean of the normal population, although measurements for the 1- to 3-year age group were significantly less than those of the older patients. Total energy intake averaged less than 86% of the recommended dietary allowances; total protein intake was more than 161% of the allowance. Nitrogen balance in 23 patients was positive and correlated most significantly with increasing energy intake (r = 0.6). Growth velocity, calculated from the interval gain during the month control period, averaged +0.3 SD, with the highest growth velocity z scores recorded for those with acquired disease. A growth velocity index, expressed as the slope of the regression between change in height SD and growth velocity z score, was used to describe the growth accomplished in the control period by age category.(ABSTRACT TRUNCATED AT 400 WORDS)

Serum osteocalcin concentrations in children with chronic renal insufficiency who are not undergoing dialysis. Growth Failure in Children with Renal Diseases Study.

This report describes the serum osteocalcin values in children with mild to moderate, but relatively stable, renal dysfunction followed in the Growth Failure in Children With Renal Diseases Study. This report is derived from data obtained during the control period (6 months) before the initiation of vitamin D therapy. Up to three measurements per patient were obtained. Serum osteocalcin concentration was compared with creatinine clearance (glomerular filtration rate) calculated by the Schwartz formula; with serum concentrations of alkaline phosphatase, parathyroid hormone, and bicarbonate; and with the percentages of the recommended dietary allowances of calories and protein ingested. By standard correlation techniques, there appeared to be an inverse correlation between calculated creatinine clearance and serum osteocalcin concentration, and a direct correlation between serum osteocalcin and parathyroid hormone values. However, when we employed a statistical technique that takes into account repeated measures in the same patient, no correlation was found between calculated glomerular filtration rate and serum osteocalcin concentration, and no direct correlation was found between serum osteocalcin and parathyroid hormone values. The lack of a correlation between calculated glomerular filtration rate and serum osteocalcin values may be due to large fluctuations in the serum osteocalcin concentration, even though renal function is relatively stable.

Convulsions in children undergoing renal transplantation.

We reviewed the records of 154 children who received 207 renal transplants for end-stage renal disease from 1965 to 1987, and discovered that 48 (31%) had had convulsive seizures, some before transplant surgery, others only after transplant, and some during both before and after transplantation. The majority of children had minimal long-term problems, and 60% of the children had only a single convulsion. In six of the patients, convulsions were a manifestation of more serious underlying conditions that produced significant morbidity. Seizures of differing clinical type occurred, with hypertension being the most significant etiologic factor. In children with renal failure, there are minimal symptoms heralding the hypertensive encephalopathy. Rapid resolution without recurrence of seizures after control of hypertension is a major sign that hypertension was the cause and that the long-term prognosis is good.