Final height in a prospective trial of late steroid withdrawal after pediatric renal transplantation treated with cyclosporine and mizoribine.

A prospective trial of corticosteroid (steroid) withdrawal after pediatric renal transplantation was started in 1990. Fifty-eight recipients with functioning grafts reached their final height. They were transplanted at a mean age of 10.7 yr. Immunosuppressive therapy with CyA, MP, and MZ was started after transplantation. MP was reduced to an alternate-day dose in 49 patients and was withdrawn in 23. Their mean height SDS was -2.4 at the time of transplantation and -2.1 at their final height. Mean final height was 157.9 cm in men and 147.6 cm in women. In 18 patients who had been withdrawn from MP for more than two yr before reaching final height, mean age at transplantation was 8.9 yr. Their mean height SDS of -2.2 at the time of transplantation increased to -1.6 at their final height (p = 0.02), and mean final height was 163.8 cm in men and 147.8 cm in women. The height SDS in all 58 patients was maintained during the immunosuppressive therapy with steroid minimization, and final height SDS increased in recipients older than five yr at transplantation with steroid withdrawal.

Urinary neutrophil-gelatinase associated lipocalin is a potential noninvasive marker for renal scarring in patients with vesicoureteral reflux.

PURPOSE: Renal scarring is a serious complication that often occurs with chronic pyelonephritis in the presence of vesicoureteral reflux. In a previous study we established a rat model of renal scarring in which we found the up-regulation of neutrophil-gelatinase associated lipocalin at the mRNA and protein levels. In this study we evaluated urinary neutrophil-gelatinase associated lipocalin as a potential biomarker for progression of renal scarring in patients with vesicoureteral reflux. MATERIALS AND METHODS: A total of 34 patients diagnosed with vesicoureteral reflux without evidence of current urinary tract infection and 28 normal healthy children were enrolled in this study. Renal scars were evaluated by (99m)technetium dimercapto-succinic acid renal scan in 24 of the reflux cases. Urinary neutrophil-gelatinase associated lipocalin levels were monitored by ELISA. RESULTS: In normal subjects urinary neutrophil-gelatinase associated lipocalin was high during infancy, decreased rapidly within the following year and reached a low stable level from age 3 years onward. Urinary neutrophil-gelatinase associated lipocalin levels, normalized to age matched standards, were significantly increased in patients with vesicoureteral reflux compared to controls. These levels did not correlate with reflux grade, but were significantly higher in patients with radiological evidence of renal scarring irrespective of reflux grade. CONCLUSIONS: Estimation of urinary neutrophil-gelatinase associated lipocalin may be useful as a noninvasive diagnostic or prognostic biomarker for renal scarring.

[Bilateral multiple ureteral polyps causing intermittent hydronephrosis: a case report].

We report an unusual case of bilateral ureteral polyps causing intermittent hydronephrosis, which developed extensively in the upper part of ureters. The patient was an 8-year-old male. He had several episodes of gross hematuria with right flank pain. Ultrasonography of the kidney showed mild bilateral hydronephrosis, while this finding was markedly aggravated in association with the onset of pain. Intravenous pyelogram and retrograde pyelogram revealed multiple filling defects in both upper parts of ureters. Since the diseased part of the ureter was wide (about 7 cm in length), a segmental resection of the right ureter with mobilization of the right kidney was performed, followed by end-to-end ureteral anastomosis. The pathological diagnosis was fibroepithelial polyps. Regarding the disease of contralateral ureter, no surgical treatment was performed because he had no clinical symptoms. Six years after the surgery, he again developed gross hematuria with left flank pain. Marked dilatation of the left renal pelvis was shown by ultrasonography, which suggested left intermittent hydronephrosis caused by ureteral polyps. He underwent a partial ureterectomy with mobilization of the left kidney for the left ureteral disease. No recurrence of polyps has been observed in the urinary tract since this surgery.

Posterior reversible encephalopathy syndrome in children: its high prevalence and more extensive imaging findings.

BACKGROUND: Posterior reversible encephalopathy syndrome is a distinctive clinicoradiological entity observed in a variety of clinical settings, including pediatric patients. A greater prevalence of this syndrome has been suggested in kidney transplant recipients and patients with kidney disease. Although usually considered benign and reversible, characteristics of this syndrome in pediatric patients remain obscure. The objective of the present study involved disclosing details of imaging findings, as well as the clinical course and prevalence of the syndrome in this field. METHODS: We investigated kidney transplant recipients and pediatric patients with kidney disease in our institution from 1990 to 2004. For these patients, clinical course, imaging findings, blood pressure, concurrent medical illnesses, and administrative condition of calcineurin inhibitors were analyzed. RESULTS: Twenty cases of posterior reversible encephalopathy syndrome were investigated in patients ranging in age from 1.9 to 18.3 years. In most patients, radiological abnormalities extended to the gray matter (17 of 20 patients), frontal and temporal lobes, and even the cerebellum (16 patients). Of 177 kidney transplant recipients (cyclosporine, 127 patients; tacrolimus, 50 patients), 6 patients administered cyclosporine (4.7%) and 4 patients administered tacrolimus (8.0%) developed the syndrome after transplantation. CONCLUSION: Posterior reversible encephalopathy syndrome should be suspected in pediatric kidney transplant recipients and patients with kidney disease if they have a sudden episode of neurological symptoms, even if imaging findings are not restricted to the subcortical white matter of the occipital region.

Unexpectedly high prevalence of pretransplant abnormal glucose tolerance in pediatric kidney transplant recipients.

Several studies suggested that the incidence of new-onset diabetes following pediatric kidney transplantation has increased markedly in recent years, with reported incidence of up to 20%. However, limited information is available regarding the incidence and features of pretransplant status of abnormal glucose tolerance in pediatric kidney transplant recipients. We assessed the risk of 55 non-diabetic pediatric transplant recipients developing PTDM by performing OGTT prior to transplantation. For post-transplant immunosuppression, each patient received either a CsA- or a TAC-based regimen. However, recipients who had abnormal glucose tolerance in the pretransplant OGTT were allocated to the CsA-based regimen. The mean age of the patients was 9.7 +/- 5.4 yr while mean BMI was 16.5 +/- 3.3 kg/m2. FPG level before transplantation was within the normal limit in all patients, while the mean HbA1C value was 4.5. However, 18 of the 55 patients (32.7%) had abnormal glucose tolerance in the pretransplant OGTT, 13 (23.6%) had impaired glucose tolerance, and 5 (9.4%) had DM. PTDM developed in two patients on the TAC-based regimen with these patients having normal glucose tolerance prior to the transplant. In contrast, the 18 patients with abnormal glucose tolerance did not develop PTDM under CsA-based immunosuppression. Our results demonstrated an unexpectedly high prevalence of abnormal glucose tolerance in pretransplant OGTT even in a pediatric population. We believe that modification of post-transplant immunosuppression by the identification of high-risk patients using the pretransplant OGTT may minimize the development of new onset of PTDM.

Gonadal Function in 15 Patients Associated with WT1 Gene Mutations.

Denys-Drash syndrome (DDS) and Frasier syndrome (FS) are caused by mutations of the WT1 gene. These disorders are characterized by renal disease, abnormality of male sex differentiation, and Wilms' tumor and gonadoblastoma. There have been few reports on gonadal function in a large series of patients with mutations of the WT1 gene. Here, we evaluated the relation between gonadal function and the phenotype of external genitalia in 15 Japanese patients with WT1 mutations. We confirmed three sets of information. First, if a diagnosis of DDS and FS is arrived at by genetic analysis, there are some overlaps in the phenotypes of external genitalia and renal complications. Second, the responses of serum T for the human CG (HCG) loading test coincided with the phenotype of external genitalia in both DDS and FS, except two patients. One DDS patient had male type external genitalia with a low level of serum T response, and one FS patient had complete female external genitalia despite a definite serum T response to HCG stimulation. Third, four FS patients had incomplete development of pubic hair, together with low DHEA-S levels.

A prospective trial of steroid withdrawal after renal transplantation treated with cyclosporine and mizoribine in children: results obtained between 1990 and 2003.

A prospective trial of adrenocorticostertoid (steroid) withdrawal after pediatric renal transplantation was begun in 1990. Ninety-four pediatric renal transplant recipients were enrolled in our multicenter study. Immunosuppressive therapy with cyclosporine (CyA), methylprednisolone (MPL), and mizoribine (MZ) was started after transplantation. MPL was reduced to administration on alternate days in 69 patients (73.4%) and was withdrawn in 27 patients (28.7%). Rejection episodes occurred in nine patients (33.3%) after withdrawal of MPL. It occurred within 3 months after withdrawal of MPL in two patients and more than 6 months in the others. Among them, two patients lost the grafts. Thirteen-year patient survival rate and graft survival rate were 94.6 and 83.1%, respectively. Forty-four of the 94 patients reached their final height. Mean final height was 155.0 cm in males and 146.3 cm in females and their height standard deviation score was -2.6 s.d., the same as that at the time of transplantation. Management of growth retardation before transplantation and further reduction in the steroid dose after transplantation will increase the final height of children with chronic renal failure.

The impact of repeated subclinical acute rejection on the progression of chronic allograft nephropathy.

Chronic allograft nephropathy (CAN) is due to both immunologic and non-immunologic factors and results in the development of nonspecific pathologic features that may even be present in long-term well-functioning renal allografts. To investigate the natural history of CAN and potential risk factors associated with progression of these histologic lesions, this study evaluated the of histologic alterations of 124 sequential protocol biopsies performed at 2, 3, and 5 yr after transplantation in 46 patients who exhibited histologic evidence of CAN in the 1-yr biopsy. The occurrence of late acute rejection (AR) greater than 4 mo posttransplant was significantly associated with the development of histologic CAN. In contrast, early clinical AR occurring within 3 mo had no impact on the subsequent development of CAN at 1 yr. Subclinical AR was evident in association with CAN in 50%, 32%, 19%, and 16% of cases with CAN at 1, 2, 3, and 5 yr, respectively. These acute lesions correlated significantly with histologic progression defined as an increased CADI score of the follow-up biopsies. Furthermore, a group of patients who exhibited repeated subclinical AR in the sequential follow-up biopsies had a lower creatinine clearance at 5 yr after transplantation and worse long-term graft survival. In contrast, the absence of evidence of acute inflammation in association with CAN at any time point was associated with minimal deterioration in renal function or progression of renal lesions during the observation period. These results suggest that the persistence of chronic active inflammation may be responsible for the histologic progression of CAN.