Ettenger Rb

Progression to end-stage renal disease in children with obstructive uropathy.

The course of 54 patients (35 boys and 19 girls) with end-stage renal disease resulting from obstructive uropathy was reviewed. The mean age at the initial sign of obstructive uropathy was 3.5 years. Twenty-two patients (41%) manifested evidence of obstructive uropathy during the first year of life. The mean age at the time of onset of ESRD (dialysis) was 12.2 years and was similar in boys and girls. The mean time interval between the first sign of obstructive uropathy and the initiation of dialysis was nine years. Fourteen patients operated upon at less than one year of age developed ESRD one to 20 years (mean ten years) following their initial surgery. Progression to ESRD occurred despite appropriate surgical management, including corrective as well as diversionary urologic procedures. However, because the patients were selectively referred for care of ESRD, no assessment of the incidence of ESRD caused by obstructive uropathy was possible. The data indicate that prolonged follow-up periods are necessary to assess the ultimate outcome of renal function in young patients with obstructive uropathy. Despite early intervention and intact renal function for many years during childhood, progression to ESRD may occur.

Focal glomerulosclerosis and renal transplantation

Eighteen patients with corticosteroid-resistant nephrotic syndrome developed end-stage renal disease and received one or more renal allografts. The lesion of focal segmental glomerulosclerosis and/or of focal glomerular obsolescence was demonstrable in the native kidneys of each patient. Following transplantation, nephrosis developed in three recipients. Two recipients developed nephrosis at two weeks and nine months posttransplant in association with rejection; the lesion of FGS was present in association with chronic rejection. Only one recipient developed recurrence of nephrosis and FGS unrelated to rejection. This was manifested by immediate onset of nephrosis in two successive allografts and histologic evidence of the lesion of FGS. The immediate recurrence in successive allografts suggests a circulating factor responsible for the renal lesion in this patient and indicates a separate etiology for a small number of patients with corticosteroid-resistant nephrosis and FGS.

Renal Transplantation in Children with Obstructive Uropathy

The outcome of renal transplantation was examined in 52 pediatric patients (mean age 13 years) whose primary renal disease was obstructive uropathy. The bladder was used at transplantation in 45 allograft recipients, 39 of whom had had a previous lower urinary tract operation or bladder defunctionalization. An ileal loop was used in 7 recipients. The 52 patients received 73 renal allografts from 58 cadaver and 15 live-related donors. Presently, 40 patients (77 per cent) have functioning allografts, 4 have returned to dialysis and 8 (15 per cent) have died. The results indicate that the outcome of renal transplantation in patients with obstructive uropathy is similar to that of other transplant recipients. Damaged and defunctionalized bladders may be used successfully in most cases. If necessary an ileal conduit is an effective alternative. Post-transplant urologic complications occur with increased frequency but with appropriate management allograft salvage and patient survival are excellent.

Minoxidil therapy in children with severe hypertension.

Six children, from 1.3 to 18 years of age, with severe hypertension associated with the hemolytic uremic syndrome, periarteritis, and renal transplant rejection received minoxidil, an antihypertensive agent, for three to 36 weeks. All had severe hypertension resistant to oral antihypertensive medications; five required frequent intravenous diazoxide therapy prior to minoxidil therapy. The mean pretreatment systolic and diastolic blood pressures were 176 and 117 mm Hg, respectively. Following treatment, the mean systolic and diastolic blood pressures were 133 and 82 mm Hg, respectively. Concomitant antihypertensive medications were decreased in all six patients once optimal blood pressure control was obtained. The initial dosage of minoxidil was 0.1 to 0.2 mg/kg/day; maximal dosage for blood pressure was 0.3 to 1.4 mg/kh/day. Major complications of therapy were fluid retention and hirsutism. Transient asymptomatic pericardial effusions occurred in two patients. Three patients on prolonged minoxidil therapy had persistent increases in right ventricular end diastolic diameters. Minoxidil is an effective oral antihypertensive agent for treatment of severe hypertension in pediatric patients. Avoidance of fluid retention is mandatory to prevent congestive heart failure.

The Clinical Impact of Humoral Immunity in Pediatric Renal Transplantation

The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study.

Renal transplantation in children less than 5 years of age.

19 young children (less than 5 years old) have received 31 renal transplants from 4 live relatives and 27 cadaver donors. The 2-year allograft survival rate for the patients receiving their 1st allograft from the 4 live donors was 75 +/- 22% while for the patients receiving their 1st allograft from 15 cadaver donors was 26 +/- 11%. 10 children are currently surviving with functioning allographs (7 cadavers and 3 live relatives); 4 have died and 5 are undergoing dialysis after the loss of at least one allograft. Despite the poor allograft survival rate the fact that 7 children are surviving with cadaver allografts indicates that the lack of a living related donor should not prevent transplants in young children.

Renal retransplantation in children

Evaluation of 75 cadaver donor retransplants revealed that the primary factor influencing allograft survival is patient responsiveness as reflected by sensitization with preformed cytotoxic antibodies. Actuarial allograft survival rates for nonpresensitized (less than 5%) and moderately presensitized (5 to 50%) recipients were significantly (P less than 0.01) better than those of highly presensitized (greater than 50%) recipients. Although HLA A&B antigen histocompatibility did not have a statistically significant effect on retransplant outcome, it appeared to influence allograft survival in the highly presensitized recipient. An approach to the management of children who lose an initial or subsequent allograft is indicated by these data.

Antibodies to donor B lymphocytes and mixed lymphocyte culture blocking in cadaveric renal transplantation.

SUMMARY In 33 renal allograft recipient-donor pairs, B and T lymphocyte complement-dependent cytotoxicity crossmatches and mixed lymphocyte culture (MLC) blocking experiments were performed and the results were correlated with graft outcome. MLC blocking, particularly in the unidirectional culture against donor-stimulating cells, was highly correlated with the presence of complement-dependent cytotoxicity antibodies against donor B lymphocytes. Grafts in both MLC blocking and B lymphocyte crossmatch-positive groups fared equally as well as those without positive tests. No difference in graft outcome was noted when the presence or absence of MLC blocking was examined in relationship to positive or negative B lymphocyte complement-dependent cytotoxicity crossmatching.

Peripheral Motor Nerve Conduction Velocities in Children Undergoing Chronic Hemodialysis

Peroneal motor nerve conduction velocities (MNCVs) were performed on 58 children aged 20 months to 12 years undergoing chronic hemodialysis. No patient had any clinical manifestations of uremic polyneuropathy. The mean MNCV in 21 children at the onset of dialysis was 42.0 m/sec; significantly slower than the control group of 51.4 +/- 5.3 m/sec (p less than 0.001). 16 studied performed between the 1st and 6th month had a mean MNCV of 43.2 +/- 5.7 m/sec, also slower than the normal controls (p less than 0.001). We conclude that peroneal MNCVs are reduced in most children at the initiation of chronic hemodialysis and do not change significantly during the next 6--12 months and that the routine practice of obtaining such studied is of no value in the clinical management of children undergoing chronic hemodialysis.

Complete Steroid Avoidance Is Effective and Safe in Children With Renal Transplants: A Multicenter Randomized Trial With Three-Year Follow-Up: Steroid-Free Therapy in Pediatric Transplantation

To determine whether steroid avoidance in pediatric kidney transplantation is safe and efficacious, a randomized, multicenter trial was performed in 12 pediatric kidney transplant centers. One hundred thirty children receiving primary kidney transplants were randomized to steroid‐free (SF) or steroid‐based (SB) immunosuppression, with concomitant tacrolimus, mycophenolate and standard dose daclizumab (SB group) or extended dose daclizumab (SF group). Follow‐up was 3 years posttransplant. Standardized height Z‐score change after 3 years follow‐up was –0.99 ± 2.20 in SF versus –0.93 ± 1.11 in SB; p = 0.825. In subgroup analysis, recipients under 5 years of age showed improved linear growth with SF compared to SB treatment (change in standardized height Z‐score at 3 years –0.43 ± 1.15 vs. –1.07 ± 1.14; p = 0.019). There were no differences in the rates of biopsy‐proven acute rejection at 3 years after transplantation (16.7% in SF vs. 17.1% in SB; p = 0.94). Patient survival was 100% in both arms; graft survival was 95% in the SF and 90% in the SB arms (p = 0.30) at 3 years follow‐up. Over the 3 year follow‐up period, the SF group showed lower systolic BP (p = 0.017) and lower cholesterol levels (p = 0.034). In conclusion, complete steroid avoidance is safe and effective in unsensitized children receiving primary kidney transplants.