Outcome after renal transplantation. Part I: intellectual and motor performance.

Comprehensive information on neurodevelopmental outcome in children and adolescents with chronic kidney disease is still limited. Intellectual performance (IP) and motor performance (MP) were systematically assessed in 27 patients at a median age of 14.1 years (range 6.5-17) and 6 years (range 0.5-12.7) after renal transplantation (RTPL). IP was analyzed with the Wechsler Intelligence Scale for Children-III (WISC-III) in 25 patients and by the Kaufman Assessment Battery for Children in two patients. MP was evaluated by the Zurich Neuromotor Assessment. Median full- scale intelligent quotient (FSIQ) was 97 (range 49-133). Twenty-one patients had an FSIQ >or= 85 (i.e. >or= mean-1 standard deviation). The five patients with neurological comorbidity had a median FSIQ of 81 (range 49-101). Verbal IQ (VIQ) (median 104; range 50-146) was significantly (p < 0.01) higher than performance IQ (PIQ) (median 88; range 48-117). The PIQ was significantly lower compared with controls (p < 0.007), and patients scored significantly lower compared with controls in five of 11 subtests of the Wechsler Scale. All MP tasks were significantly (p < 0.01) lower than in controls, and also in children without neurological comorbidity. Socioeconomic status was significantly correlated with FSIQ (p = 0.03). IP after RTPL was within the normal range for the majority of children. PIQ was lower compared with VIQ, and MP was significantly affected in all children after RTPL.

Outcome after renal transplantation. Part II: quality of life and psychosocial adjustment.

Knowledge of health-related quality of life (QOL) and psychosocial adjustment (PA) in children after renal transplantation (RTPL) is limited. QOL and PA were evaluated by standardized tests in patients after RTPL. Thirty-seven children of median age 14.5 years (range 6.5-17 years) were investigated a mean 4.5 years (range 0.5-12.8 years) after RTPL. Child- and parent-rated QOL was evaluated with the Child Quality of life Questionnaire of The Netherlands Organization for Applied Scientific Research Academical Medical Centre (TNO-AZL). PA was assessed by the Child Behaviour Checklist (CBCL) providing parental reports of a child's behaviour. In patients' self-ratings, the QOL dimension physical complaints (P < 0.0005) scored significantly better than that of healthy controls, whereas the dimension positive emotional functioning was impaired (P = 0.02). Parents rated motor functioning (P = 0.002), autonomy (P = 0.01), cognition (P = 0.04) and positive emotions (P < 0.0005) as significantly impaired. Parents also assessed PA significantly (P = 0.02) impaired with regard to internalizing behaviour. Dialysis duration, young age at RTPL, living-related donation, steroid treatment, adverse family relationships and maternal distress had a significantly negative impact on QOL and PA (P < 0.05). Patients rated QOL higher than did healthy controls. Parents evaluated their children's QOL and PA more pessimistically than did the patients themselves. Both illness-related variables and family environment played an important role.

Selective late steroid withdrawal after renal transplantation.

Steroid withdrawal (SW) after paediatric renal transplantation (RTPL) is controversial. Selective late SW has been performed in our unit since 1995. The safety and effects of SW were analysed retrospectively in 47 patients undergoing RTPL between 1995 and 2004. Initial immunosuppression consisted of cyclosporine A, azathioprine or mycophenolate mofetil and steroids. Criteria for SW were: (1) stable renal function, (2) time interval after RTPL > or = 1 year, (3) no rejection or time interval after last rejection > or = 1 year and (4) good compliance. SW was performed in 30 patients at an age of 13.5 years (range 4.5-18.5) and 2.2 years (range 1-6.6) after RTPL. After SW, one patient experienced a steroid-sensitive rejection. Follow-up after SW (1.3 year; range 0.25-7.5) showed maintained renal function: glomerular filtration rate at SW and currently was 82 (65-128) and 82 (42-115) ml/min per 1.73 m(2), respectively. The number of patients on antihypertensive treatment did not significantly change (at SW: n = 15; currently: n = 11). Height and body mass index (BMI) remained stable: Median standard deviation score (SDS) for height/BMI at SW and currently was -1.1/0.2 and -0.8/0.1, respectively. Selective late SW was safe regarding renal function and had no significant effect on blood pressure and growth.

Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy.

CAN is a major cause for allograft loss in renal transplantation. Sirolimus was recently introduced as a potent non-nephrotoxic alternative to CNIs. In the present study, effects of a conversion protocol were investigated in pediatric CAN with declining GFR, defined by a Schwartz formula clearance below 60 mL/1.73 m2/min, steadily increasing SCr and allograft biopsy. In eight children with a median age of 12.8 yr, sirolimus was started at median 32 months after transplantation with a loading dose of 0.24 mg/kgBW, followed by 0.2 mg/kgBW/day, aimed at trough levels of 15-20 ng/mL. CNIs were reduced to 50% at start of sirolimus and discontinued at median seven days when target levels of sirolimus were reached. Following conversion, changes of GFR significantly stabilized (-2.9 vs. +0.4 mL/min/1.73 m2/month, p = 0.025). Individual GFR increased in five of eight patients (p = 0.026), only one child exhibited unaltered progression of graft failure. In the responders, mean SCr improved by 0.3 mg/dL (p = 0.043). Effects were not dependent on GFR at conversion, nor time post-transplantation. Blood pressure, hematological parameters and proteinuria remained stable during the observation period, serum lipids transiently increased. About half of the children suffered from infectious complications. No child had to be taken off sirolimus; there was no graft loss during the observation period. In conclusion, conversion from CNIs to sirolimus is an effective protocol with tolerable side effects to stabilize renal graft function for at least one yr in the majority of children with biopsy proven CAN.

Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy.

Chronic allograft nephropathy is a major cause for allograft loss in renal transplantation. Sirolimus was recently introduced as a potent non-nephrotoxic alternative to calcineurin inhibitors. In the present study, effects of a conversion protocol were investigated in pediatric chronic allograft nephropathy with declining glomerular filtration rate (GFR), defined by a Schwartz formula clearance below 60 mL/1.73 m(2)/min, steadily increasing serum creatinine and allograft biopsy. In eight children with a median age of 12.8 yr, sirolimus was started at median 32 months after transplantation with a loading dose of 0.24 mg/kg bodyweight (BW), followed by 0.2 mg/kgBW/day, aimed at trough levels of 15-20 ng/mL. Calcineurin inhibitors were reduced to 50% at the start of sirolimus and discontinued at median 7 days when target levels of sirolimus were reached. Following conversion, changes of GFR significantly stabilized (-2.9 vs. +0.4 mL/min/1.73 m(2)/month, p = 0.025). Individual GFR increased in five out of eight patients (p = 0.026), and only one child exhibited unaltered progression of graft failure. In the responders, mean serum creatinine improved by 0.3 mg/dL (p = 0.043). Effects were not dependent on GFR at conversion, or on time post-transplantation. Blood pressure, hematological parameters and proteinuria remained stable during the observation period, and serum lipids increased transiently. About half of the children suffered from infectious complications. No child had to be taken off sirolimus; there was no graft loss during the observation period. In conclusion, conversion from calcineurin inhibitors to sirolimus is an effective protocol with tolerable side effects to stabilize renal graft function for at least one yr in the majority of children with biopsy-proven chronic allograft nephropathy.

No evidence for hyperhomocysteinemia or increased prevalence of genetic polymorphisms in the homocysteine pathway in patients with moderate juvenile idiopathic arthritis.

OBJECTIVE: Elevated plasma total homocysteine (tHcy) concentrations are associated with premature cardiovascular disease. We assessed tHcy, folate, vitamin B12 (Vit B12), vitamin B6 (Vit B6), and genetic polymorphisms potentially enhancing tHcy in patients with juvenile idiopathic arthritis (JIA) and healthy controls. METHODS: Open study of 56 consecutive patients with JIA and 62 controls. RESULTS: tHcy concentrations were normal in JIA patients (mean 6.5 +/- 2 micromol/l) and controls (mean 7.5 +/- 2.2 micromol/l). Folate concentrations were significantly higher in JIA patients (40.2 +/- 67.9 ng/ml) compared to controls (13.6 +/- 8.2 ng/ml). The prevalence of genetic polymorphisms coding for key enzymes in the homocysteine pathway did not differ between patients and controls. Erythrocyte sedimentation rate (ESR) showed significant inverse correlations with circulating Vit B6 and tHcy concentrations. CONCLUSION: No evidence for hyperhomocysteinemia or evidence for a specific genetic predisposition for hyperhomocysteinemia was present in patients with JIA. Elevated ESR is not associated with hyperhomocysteinemia.

[Referral to the pediatric dialysis unit -- the earlier the better?]. / Zuweisung an die Kinderdialyse -- Ist früher besser?

Whereas recent research has demonstrated clear evidence for beneficial effects of early referral to the nephrologist in chronic renal insufficiency in adults, no such data exist for the pediatric population. In this study, we therefore correlated patient age and residual renal function at first presentation to a specialized pediatric nephrologist with the extent of secondary uremic complications and the further course of renal function. From March 2003 until March 2004, 43 children (34 boys, aged 10.1 +/- 6.3 yrs) with congenital-urologic (n = 26), congenital-nephrologic (n = 13) or acquired (n = 4) renal diseases had been followed for 3.9 yrs (14 days to 17.5 yrs) at the Kinderdialyse Wien, with a residual renal function of 35 +/- 20.5 ml/min/1.73 m(2) at first presentation. With regards to uremic secondary complications, the majority of children exhibited involvement of at least two systems at first presentation. Thereafter, children with congenital diseases who were referred to the specialized pediatric nephrology unit within the first year of live demonstrated a significantly better course of residual renal function (1.8% vs -0.7%, p = 0.034) than children who were referred later. These data confirm recent registry reports on chronic renal insufficiency in children. Only about a third of the children of our population were presented to a specialized pediatric nephrology center within their first year of life (despite a congenital disease in 90% of them). Thus, therapeutic interventions might be currently offered at a delayed time point in the majority of children.

Feasibility of long-term intraventricular therapy with mafosfamide (n = 26) and etoposide (n = 11): experience in 26 children with disseminated malignant brain tumors.

Treatment options for leptomeningeal disseminated brain tumors are limited by the lack of effective drugs for intrathecal therapy of non-hematologic malignancies. We report on our experience with an intraventricular therapy consisting of mafosfamide, a preactivated cyclophosphamide derivative, and etoposide. Between May 1994 and 2002, 26 patients aged 2-19 years with various intensely pretreated disseminated brain tumors received intraventricular mafosfamide via an indwelling subcutaneous reservoir. Twenty-three of them received a dose of 20 mg. Mafosfamide was administered once or twice weekly until remission was achieved and every 2-6 weeks thereafter as maintenance therapy for a total of 736 administrations (2-63/patient). Since March 1998, two patients were switched to receive intraventricular etoposide and nine received etoposide alternating with mafosfamide. Etoposide was given at a dose of 0.5 mg x 5 d every 3-6 weeks for a total of 122 courses (1-29/patient). Immediate toxicities such as transient headaches, nausea, and vomiting occurred with mafosfamide but were manageable with premedication. Etoposide did not cause any discomfort. No long-term toxicities attributable to intrathecal therapy as evidenced by magnetic resonance imaging or neurologic evaluation were observed. Since all patients received some sort of concurrent anti-cancer therapy, the efficacy of intrathecal therapy cannot be assessed independently. However, seven of 13 patients evaluable for response by cerebrospinal fluid (CSF) cytology developed CSF dissemination under systemic chemotherapy and cleared their CSF only after administration of intrathecal mafosfamide. In conclusion, intraventricularly administered mafosfamide at a dose of 20 mg and etoposide at a dose of 0.5 mg x 5 d for patients over 2 years of age are feasible and safe and may produce responses.

Patterns of joint involvement at onset differentiate oligoarticular juvenile psoriatic arthritis from pauciarticular juvenile rheumatoid arthritis.

OBJECTIVE: To compare the patterns of joint involvement of patients with oligoarticular onset juvenile psoriatic arthritis (Oligo-JPsA) and pauciarticular onset juvenile rheumatoid arthritis (Pauci-JRA) in order to estimate the predictive performance of specific patterns for the diagnosis of Oligo-JPsA. METHODS: Twenty-three children who fulfilled the diagnostic criteria for JPsA (Vancouver criteria) and who had fewer than 5 joints involved in the first 6 months of disease (Oligo-JPsA), and 64 children with Pauci-JRA (ACR criteria) were enrolled. Patients were also classified with respect to the ILAR criteria for juvenile idiopathic arthritis (JIA). Patient characteristics and clinical features at onset and during followup were determined. Patterns of joint involvement at onset of disease and their ability to differentiate between Oligo-JPsA and Pauci-JRA/Oligo-JIA were evaluated. RESULTS: Small joint disease (defined as involvement of any of the metatarsophalangeal or proximal or distal interphalangeal joints of the foot, or metacarpophalangeal or proximal or distal interphalangeal joints of the hand) was significantly more frequent in Oligo-JPsA than in Pauci-JRA at disease onset. The odds of patients with Oligo-JPsA having small joint disease or wrist disease within 6 months of disease onset were much higher than those with Pauci-JRA or Oligo-JIA (p < 0.05 or 0.001). CONCLUSION: Small joint disease and wrist disease are suggestive of Oligo-JPsA. The use of a criterion consisting of small joint disease and/or wrist disease and/or dactylitis instead of dactylitis alone may increase the ability to differentiate Oligo-JPsA from Pauci-JRA or Oligo-JIA.