The IGF/IGFBP system in relation to macroscopic bone architecture in pediatric renal transplant patients.

The post-transplant bone disease of the peripheral skeleton in pediatric renal transplant recipients is characterized by an inadequately thin bone cortex in relation to muscular force. A major hormonal modulator of periosteal growth is the insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system. We therefore hypothesized that the reduced cortical thickness in these patients may be due to functional IGF deficiency. To test this hypothesis, we investigated 55 patients (mean estimated glomerular filtration rate 86.3 +/- 30.0 ml/min/1.73 m(2)) in a cross-sectional study. Parameters of macroscopic bone architecture and forearm muscle size were analyzed by peripheral quantitative computed tomography (pQCT), and serum IGF/IGFBP system components were measured by specific radioimmunoassays. The mean (+/- standard deviation) standardized serum IGF-I (0.20 +/- 1.16 score) level was normal, while the mean IGF-II (1.16 +/- 0.11 score) level was significantly elevated. Serum IGFBP-1 and IGFBP-2 levels were not altered, whereas the IGFBP-3 (1.34 +/- 0.15 score) level was significantly increased. The serum IGFBP-4 level was slightly elevated (by 11%), the IGFBP-6 level was markedly (2.3-fold) elevated, while the IGFBP-5 level was comparable to that of the control. The respective age-adjusted cortical thickness at both the proximal (r = 0.407, P < 0.005) and distal (r = 0.383, P < 0.01) forearm was positively correlated with the standardized serum IGF-I level. In conclusion, the serum IGF/IGFBP system in pediatric renal transplant recipients is characterized by an increase in the levels of the inhibitory IGFBPs, IGFBP-3, -4 and -6, resulting in a functional IGF deficiency. The positive correlation of IGF-I with cortical thickness underlines the importance of this hormonal system in the modeling of bone, particularly periosteal growth.

Successful interventional treatment of arteriovenous fistula after kidney biopsy in pediatric patients--a report of three cases.

BACKGROUND: With an incidence of up to 16%, arteriovenous fistula (AVF) is a frequent complication after renal biopsy. METHODS: We report on three cases, where renal biopsy in pediatric and adolescent patients led to various but clinically significant complications. In each patient two cores of renal parenchyma from the upper pole of the renal transplant or the lower pole of the right native kidney, respectively, were obtained with two attempts. RESULTS: Immediate post-bioptic ultrasound did not show any abnormalities. Setting of an AVF was suspected when complications occurred and ultrasound and Doppler studies showed AVF. The diagnosis was confirmed by angiography and occlusion of the fistulae was performed in the same session. CONCLUSION: We conclude that persistent AVF is an uncommon but serious complication after renal biopsy. Well-timed angiography when AVF is suspected can prevent loss of function, especially in transplant recipients.

Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome.

OBJECTIVE: Long-term outcome of steroid-sensitive idiopathic nephrotic syndrome (SSNS) in children is usually considered benign, although data on follow-up into adulthood are scarce. The aim of this study was to investigate adults who had childhood SSNS regarding their relapse rate, growth, and renal and extrarenal morbidity. STUDY DESIGN: Adult patients (n=42, 26 males) were evaluated at a median age of 28.0 (18.1 to 46.9) years and a median follow-up of 22.0 (2.9 to 39.0) years since diagnosis. RESULTS: Fourteen of 42 (33%) patients relapsed in adulthood. The number of relapses during childhood and adolescence and a complicated course-administration of steroid-sparing medication such as cyclophosphamide, chlorambucil, and cyclosporin A-were identified as risk factors. Final adult height (median SD score -0.4, range -3.3 to +1.3) and body mass index (BMI) were normal. Renal function was normal in all patients, and overall morbidity was low. Only eight patients (three males) had children. Cytotoxic therapy was identified as a major factor contributing to childlessness. CONCLUSION: Relapses in adulthood were common in pediatric patients with SSNS. Growth and renal function were normal, and overall morbidity was low. Yet, transition to an adult nephrologist is recommended for all children with relapsing SSNS.

Health-related quality of life and psychosocial adjustment in steroid-sensitive nephrotic syndrome.

OBJECTIVES: To evaluate quality of life (QOL) and psychosocial adjustment by standardized tests in well-characterized patients with steroid-sensitive nephrotic syndrome. STUDY DESIGN: Forty-five patients were investigated at a median age of 9.8 years (range, 3.4 to 19.8) and 5.9 years (range, 0.1 to 16.3) since diagnosis. Child- and parent-rated QOL was evaluated by the The Netherlands Organization for Applied Scientific Research Academical Medical Center (TNO-AZL) Child Quality of life Questionnaire. Psychosocial adjustment was assessed by the Child Behavior Checklist and the Teacher Report Form. RESULTS: In patients, only the QOL subscale "social functioning" was impaired compared with that in control subjects, whereas parents rated 4 of a total of 7 subscales as abnormal. Psychosocial adjustment was impaired at home and at school. Steroid dependency and cytotoxic treatment had a significant negative impact on QOL only, whereas family climate, especially maternal distress, negatively affected both QOL and psychosocial adjustment. CONCLUSIONS: QOL and psychosocial adjustment are impaired in steroid-sensitive nephrotic syndrome. Both illness-related variables and family climate play an important role.

Analysis of the functional muscle-bone unit of the forearm in pediatric renal transplant recipients.

BACKGROUND: Renal transplantation in children and adolescents is associated with various skeletal complications. The incidence of spontaneous fractures appears to be increased, but the reasons for this are not entirely clear. Our objective was therefore to evaluate macroscopic bone architecture, mass, and strength by peripheral quantitative computed tomography (pQCT), a method that is not influenced by size-related artifacts. In addition, we investigated the muscle-bone relationship in these patients because under physiologic conditions bone strength continually adapts to increasing mechanical loads, that is, muscle force. METHODS: In 55 patients (41 males) aged 15.8 +/- 4.1 years, we evaluated in a cross-sectional study 4.9 +/- 3.6 years after renal grafting bone mass, density, geometry, and strength of the radius, as well as forearm muscle size and strength, using pQCT at the proximal and distal radius, radiography of the second metacarpal shaft and hand dynamometry. Data were compared to a large cohort (N= 350) of healthy children. RESULTS: Muscle mass and force were adequate for body size in pediatric renal transplant recipients. However, the radial bone was characterized by an inadequately thin cortex in relation to muscular force, as shown by a reduced height-adjusted cortical thickness both at the proximal (-0.83 +/- 1.12 SDS) and distal radius (-0.52 +/- 1.69 SDS), the metacarpal shaft (-0.54 +/- 1.35 SDS), and by a reduced relative cortical area (-0.90 +/- 1.13 SDS), while the mineralization of trabecular bone was unaltered. As a consequence of cortical thinning, the Strength-Strain Index that reflects the combined strength of trabecular and cortical bone was reduced in these patients. CONCLUSION: While bone mineral density of the forearm is not decreased in pediatric renal transplant recipients, bone strength in relation to muscular force is reduced. This alteration may contribute to the increased propensity for fractures in these patients.