Assessment of dual-energy X-ray absorptiometry measures of bone health in pediatric chronic kidney disease.

BACKGROUND: Dual-energy X-ray absorptiometry (DXA) techniques are limited in childhood chronic kidney disease (CKD) by the confounding effect of short stature and opposing parathyroid hormone effects on trabecular and cortical bone. Peripheral quantitative computed tomography (pQCT) is not subject to these limitations. METHODS: Lumbar spine (LS) and whole-body (WB) DXA and tibia pQCT scans were obtained in 88 stage 4-5 CKD and >650 healthy participants, ages 5-21 years. Sex- and race-specific Z-scores were generated for bone mineral density (BMD) and bone mineral content (BMC) by DXA, relative to age and adjusted for height Z-score (LS-BMD-Z and WB-BMC-Z), and compared to pQCT Z-scores for trabecular BMD (TrabBMD-Z) for age and cortical BMC (CortBMC-Z) for age and tibia length. RESULTS: LS-BMD-Z [0.50 (95% C.I. 0.28, 0.73), p<0.0001] and TrabBMD-Z [0.53 (0.27, 0.79), p<0.0001] were greater in CKD, and WB-BMC-Z [-0.36 (-0.53, -0.19), p<0.0001] and CortBMC-Z [-0.48 (-0.70, -0.27), p<0.0001] were lower, compared to reference participants. Z-scores were correlated at trabecular (LS-BMD-Z and TrabBMD-Z: R=0.36) and cortical (WB-BMC-Z and CortBMC-Z: R=0.64) sites in CKD; similar to correlations in reference participants. CONCLUSIONS: Lumbar spine and whole-body DXA suggested greater trabecular BMD and lower cortical BMC in CKD, consistent with pQCT results; however, correlations were modest. Studies are needed to identify methods that predict fracture in childhood CKD.

Bone density and cortical structure after pediatric renal transplantation.

The impact of renal transplantation on trabecular and cortical bone mineral density (BMD) and cortical structure is unknown. We obtained quantitative computed tomography scans of the tibia in pediatric renal transplant recipients at transplantation and 3, 6, and 12 months; 58 recipients completed at least two visits. We used more than 700 reference participants to generate Z-scores for trabecular BMD, cortical BMD, section modulus (a summary measure of cortical dimensions and strength), and muscle and fat area. At baseline, compared with reference participants, renal transplant recipients had significantly lower mean section modulus and muscle area; trabecular BMD was significantly greater than reference participants only in transplant recipients younger than 13 years. After transplantation, trabecular BMD decreased significantly in association with greater glucocorticoid exposure. Cortical BMD increased significantly in association with greater glucocorticoid exposure and greater decreases in parathyroid hormone levels. Muscle and fat area both increased significantly, but section modulus did not improve. At 12 months, transplantation associated with significantly lower section modulus and greater fat area compared with reference participants. Muscle area and cortical BMD did not differ significantly between transplant recipients and reference participants. Trabecular BMD was no longer significantly elevated in younger recipients and was low in older recipients. Pediatric renal transplant associated with persistent deficits in section modulus, despite recovery of muscle, and low trabecular BMD in older recipients. Future studies should determine the implications of these data on fracture risk and identify strategies to improve bone density and structure.

Vitamin D deficiency is common in children and adolescents with chronic kidney disease.

Here we determined if vitamin D deficiency is more common in children with chronic kidney disease compared to healthy children. In addition, we sought to identify disease-specific risk factors for this deficiency, as well as its metabolic consequences. We found that nearly half of 182 patients (ages 5 to 21) with kidney disease (stages 2 to 5) and a third of age-matched 276 healthy children were 25-hydroxyvitamin D deficient (<20 ng/ml). The risk of deficiency was significantly greater in advanced disease. Focal segmental glomerulosclerosis and low albumin were significantly associated with lower 25-hydroxyvitamin D, which, in turn, was associated with significantly higher intact parathyroid hormone levels. We found that 25-hydroxyvitamin D levels were positively associated with 1,25-dihydroxyvitamin D, the relationship being greatest in advanced disease (significant interaction), and inversely related to those of inflammatory markers C-reactive protein and IL-6. The association with C-reactive protein persisted when adjusted for the severity of kidney disease. Thus, lower 25-hydroxyvitamin D may contribute to hyperparathyroidism, inflammation, and lower 1,25-dihydroxyvitamin D in children and adolescents, especially those with advanced kidney disease.

Early volume expansion during diarrhea and relative nephroprotection during subsequent hemolytic uremic syndrome.

OBJECTIVES: To determine if interventions during the pre-hemolytic uremic syndrome (HUS) diarrhea phase are associated with maintenance of urine output during HUS. DESIGN: Prospective observational cohort study. SETTINGS: Eleven pediatric hospitals in the United States and Scotland. PARTICIPANTS: Children younger than 18 years with diarrhea-associated HUS (hematocrit level <30% with smear evidence of intravascular erythrocyte destruction), thrombocytopenia (platelet count <150 × 10³/mm³), and impaired renal function (serum creatinine concentration > upper limit of reference range for age). INTERVENTIONS: Intravenous fluid was given within the first 4 days of the onset of diarrhea. OUTCOME MEASURE: Presence or absence of oligoanuria (urine output ≤ 0.5 mL/kg/h for >1 day). RESULTS: The overall oligoanuric rate of the 50 participants was 68%, but was 84% among those who received no intravenous fluids in the first 4 days of illness. The relative risk of oligoanuria when fluids were not given in this interval was 1.6 (95% confidence interval, 1.1-2.4; P = .02). Children with oligoanuric HUS were given less total intravenous fluid (r = -0.32; P = .02) and sodium (r = -0.27; P = .05) in the first 4 days of illness than those without oligoanuria. In multivariable analysis, the most significant covariate was volume infused, but volume and sodium strongly covaried. CONCLUSIONS: Intravenous volume expansion is an underused intervention that could decrease the frequency of oligoanuric renal failure in patients at risk of HUS.

Volumetric bone mineral density and bone structure in childhood chronic kidney disease.

Chronic kidney disease (CKD) is associated with increased fracture risk and skeletal deformities. The impact of CKD on volumetric bone mineral density (vBMD) and cortical dimensions during growth is unknown. Tibia quantitative computed tomographic scans were obtained in 156 children with CKD [69 stages 2 to 3, 51 stages 4 to 5, and 36 stage 5D (dialysis)] and 831 healthy participants aged 5 to 21 years. Sex-, race-, and age- or tibia length-specific Z-scores were generated for trabecular BMD (TrabBMD), cortical BMD (CortBMD), cortical area (CortArea) and endosteal circumference (EndoC). Greater CKD severity was associated with a higher TrabBMD Z-score in younger participants (p < .001) compared with healthy children; this association was attenuated in older participants (interaction p < .001). Mean CortArea Z-score was lower (p < .01) in CKD 4-5 [-0.49, 95% confidence interval (CI) -0.80, -0.18)] and CKD 5D (-0.49, 95% CI -0.83, -0.15) compared with healthy children. Among CKD participants, parathyroid hormone (PTH) levels were positively associated with TrabBMD Z-score (p < .01), and this association was significantly attenuated in older participants (interaction p < .05). Higher levels of PTH and biomarkers of bone formation (bone-specific alkaline phosphatase) and resorption (serum C-terminal telopeptide of type 1 collagen) were associated with lower CortBMD and CortArea Z-scores and greater EndoC Z-score (r = 0.18-0.36, all p ≤ .02). CortBMD Z-score was significantly lower in CKD participants with PTH levels above versus below the upper limit of the Kidney Disease Outcome Quality Initiative (KDOQI) CKD stage-specific target range: -0.46 ± 1.29 versus 0.12 ± 1.14 (p < .01). In summary, childhood CKD and secondary hyperparathyroidism were associated with significant reductions in cortical area and CortBMD and greater TrabBMD in younger children. Future studies are needed to establish the fracture implications of these alterations and to determine if cortical and trabecular abnormalities are reversible.

Vitamin D deficiency and parathyroid hormone levels following renal transplantation in children.

The objectives were to determine the prevalence of vitamin D deficiency [25(OH)D < 10 ng/ml] in pediatric renal transplant (RTx) recipients, compared with controls and identify correlates of changes in 25(OH)D and intact parathyroid hormone (iPTH) levels following transplantation. Serum 25(OH)D, 1,25(OH)(2)D, and iPTH were measured once in 275 healthy controls and at transplantation, and 3 and 12 months posttransplantation in 58 RTx recipients. Multivariate logistic regression models determined the odds ratio (OR) of vitamin D deficiency in RTx recipients vs. controls adjusted for age, sex, race, and season. Generalized estimating equations were used to assess changes following transplantation. At transplantation, 22% of nonblack and 27% of black RTx recipients were vitamin D deficient. The adjusted OR of vitamin D deficiency was greater in RTx recipients (p < 0.001) compared with controls; however, the transplant association was greater in nonblack vs. black individuals (interaction p = 0.02). Overall, 25(OH)D levels did not change significantly following transplantation. Younger age (p < 0.01), nonblack race (p < 0.001), visits in nonwinter months (p < 0.001), and supplementation with ≥400 IU/day ergo/cholecalciferol (p < 0.001) were associated with increases (or lesser declines) in 25(OH)D following transplantation. Increases in 25(OH)D levels (p < 0.001) and vitamin D supplementation (p < 0.01) were associated with greater reductions in iPTH levels following transplantation, independent of 1,25(OH)(2)D levels.

Multicenter study of effects of pediatric peritoneal dialysis practices on bacterial peritonitis.

Bacterial peritonitis is a major cause of morbidity in pediatric peritoneal dialysis (PD) patients and can lead to catheter removal, hospitalizations, peritoneal membrane dysfunction, and sepsis. The goal of this prospective study was to determine whether the incidence of peritonitis had improved over time and what practice patterns influenced peritonitis. Two cohorts of PD patients within the End-stage Renal Disease (ESRD) Networks 9/10 and who were <21 years old were prospectively followed for 1 year in 1991 and 2002 and included 70 and 82 patients, respectively. A questionnaire was completed for each patient outlining demographic, clinical, and dialysis characteristics. A second questionnaire was completed for each peritonitis episode. The 2002 cohort was younger, included more nonwhites, and had fewer peritonitis episodes. A shift in practice patterns was evident, with more of the 2002 cohort receiving prophylactic antibiotics and omentectomy at catheter insertion and using cycler machines with a parent operator. Peritonitis-free interval was 10.8 months in 1991 and 17.3 months in 2002. The only variable statistically related to the lower rate of peritonitis in 2002 was fewer prior peritonitis events. The results show an improvement in peritonitis-free interval in studied patients on PD, which appears to be related to numerous changes in practice patterns.

Renal function in infants with sickle cell anemia: baseline data from the BABY HUG trial.

OBJECTIVES: To examine the feasibility and accuracy of glomerular filtration rate (GFR) measurements in infants with sickle cell anemia (SCA). STUDY DESIGN: The NHLBI/NICHD-sponsored Phase III randomized double-blinded placebo-controlled trial (BABY HUG) tests the hypothesis that hydroxyurea can prevent chronic organ damage in SCA. GFR elevation is a coprimary endpoint, measured quantitatively by technetium 99m-labeled diethylenetriaminepentaacetic acid (DTPA) plasma clearance and estimated by the Schwartz equation with height and creatinine. RESULTS: Baseline DTPA GFR measurement was attempted in 191 infants; 176 of 184 completed studies (96%) were interpretable. Average age (mean +/- 1SD) was 13.7 +/- 2.6 months. Average DTPA GFR was 125.2 +/- 34.4 (range 40.2-300.9, normal 91.5 +/- 17.8 mL/min/1.73m(2)), while Schwartz estimates were higher at 184.4 +/- 55.5 mL/min/1.73m(2). DTPA GFR was correlated with Schwartz GFR (r(2) = 0.0658, P = .0012); also with age, weight, height, and kidney volume (all P < .002); but not with hemoglobin, HbF, white blood cell count, reticulocytes, medical events, or splenic function. CONCLUSIONS: Quantitative GFR measurement is feasible but variable among infants with SCA. Schwartz GFR estimates are not highly correlated with quantitative DTPA GFR values. Baseline GFR measurements suggest that renal dysfunction in SCA, evidenced by glomerular hyperfiltration, begins during infancy.

Anatomic distribution of renal artery stenosis in children: implications for imaging.

BACKGROUND: Renal artery stenosis (RAS) causes significant hypertension in children. Frequently, pediatric RAS occurs with systemic disorders. In these cases, stenoses are often complex and/or include long segments. We believed that hypertensive children without comorbid conditions had a different lesion distribution and that the difference might have implications for imaging and treatment. OBJECTIVE: To identify locations of RAS lesions in these hypertensive children without comorbid conditions. MATERIALS AND METHODS: Patients who had renal angiography for hypertension from 1993 to 2005 were identified. Patients with systemic disorders, renovascular surgery, or normal angiograms were excluded. The angiograms of the remaining patients were reviewed for number, type, and location of stenoses. RESULTS: Eighty-seven patients underwent renal angiography for hypertension; 30 were excluded for comorbid conditions. Twenty-one of the remaining 57 patients had abnormal angiograms; 24 stenoses were identified in those patients. All were focal and distributed as follows: 6 (25%) main renal artery, 12 (50%) 2nd order branch, 3 (12.5%) 3rd order branch, and 3 (12.5%) accessory renal artery. CONCLUSION: Hypertensive children without comorbid conditions who have RAS usually have single, focal branch artery stenoses. This distribution supports angiography in these patients because of its superior sensitivity in detecting branch vessel disease and its therapeutic role in percutaneous transluminal renal angioplasty.

Increasing incidence of post-kidney transplant anemia in children.

Anemia status at 1-year post-kidney transplant was documented retrospectively in 231 pediatric recipients (mean age: 12.6 +/- 5.0, range: 1.9-20.7 years) at Cincinnati Children's Hospital Medical Center between 1978 and 2003. Anemia was present in 59 (25.5%) patients. The prevalence of anemia has increased in the more recent eras (1978-1985: 7.8%, 1986-1997: 29%; 1998-2003: 32%, p < 0.01). Logistic regression analysis determined that the use of calcineurin inhibitors or impaired allograft function predicted anemia at 1-year post-transplant. Kaplan-Meier analysis showed that children with anemia at 1-year post-transplant had a significantly worse overall allograft survival than children without anemia (p = 0.02). However, when data were analyzed using a Cox proportional hazards model, only lower allograft function at 1-year post-transplant, black race and older era, but not anemia, independently predicted worse graft survival in children. This study suggests that the recent increase in the incidence of anemia post-kidney transplant is related to modern immunosuppressive therapy and that post-transplant anemia is more likely a marker of allograft dysfunction in children rather than its cause.

Recurrence of membranoproliferative glomerulonephritis type II in renal allografts: The North American Pediatric Renal Transplant Cooperative Study experience.

Membranoproliferative glomerulonephritis type II (MPGN II) is an uncommon form of complement-dependent acquired renal disease. Although it has been recognized since the 1970s that MPGN II recurs almost universally in renal transplants, data regarding the long-term consequences of disease recurrence are limited. Therefore, a retrospective comparative analysis of 75 patients with MPGN II contained in the North American Pediatric Renal Transplant Cooperative Study transplantation database was performed. Five-year graft survival for patients with MPGN II was significantly worse (50.0 +/- 7.5%) compared with the database as a whole (74.3 +/- 0.6%; P < 0.001). Living related donor organs had a significantly better 5-yr survival (65.9 +/- 10.7%) compared with cadaveric donor organs (34.1 +/- 9.8%; P = 0.004). The primary cause of graft failure in 11 (14.7%) patients was recurrent disease. Supplemental surveys were obtained on 29 (38%) of 75 patients. Analysis of these data indicated that recurrent disease occurred in 12 (67%) of the 18 patients with posttransplantation biopsies. Although there was no correlation between pretransplantation presentation, pre- or posttransplantation C3 levels, and either disease recurrence or graft failure, there was a strong association between heavy proteinuria and disease recurrence. The presence of glomerular crescents in allograft biopsies had a significant negative correlation with graft survival. At last follow-up, patients with recurrent disease had significantly higher serum creatinine and qualitatively more proteinuria than patients without biopsy-proven disease. These data indicate that recurrent MPGN II has a significant negative impact on renal allograft function and survival.

Comparison of vascular access type in pediatric hemodialysis patients with respect to urea clearance, anemia management, and serum albumin concentration.

BACKGROUND: Central venous catheters (CVCs) remain the most common vascular access in pediatric hemodialysis patients. Risks for infection and dysfunction are greatest among patients using CVCs as opposed to those with arteriovenous fistulae (AVFs) and arteriovenous grafts (AVGs). Studies of adult hemodialysis patients show greater morbidity and mortality in patients with a CVC. The study goal is to determine whether hemodialysis access in pediatric patients influences urea clearance (Kt/V and urea reduction rate [URR]), anemia management (hemoglobin [Hgb] concentration and recombinant human erythropoietin [rHuEPO] use), and serum albumin levels. METHODS: Data were abstracted from The Renal Network, Inc, Data System for pediatric patients with identified hemodialysis access from 2000 to 2002. Data were subdivided according to age: 0 to 5, 6 to 10, 11 to 15, and 16 to 18 years. Univariate analysis of variance was performed on Kt/V, URR, serum albumin concentration, Hgb concentration, and rHuEPO dose. RESULTS: There were 601 recorded observations in 140 patients (90 males and 50 females). There were 56 Caucasians and 73 African Americans. Comparing Kt/V and URR, adjusting for blood flow and treatment times, a difference between AVFs and AVGs compared with CVCs was seen. Mean Hgb concentration was lower in patients with a CVC. Mean rHuEPO dose was greatest in patients using a CVC, and mean albumin level was lower for patients using a CVC. CONCLUSION: In children, hemodialysis using an AVF or AVG improves outcome in relation to urea clearance, Hgb concentration, and serum albumin level. Efforts to reduce CVC use should be extended to the pediatric dialysis population.

Trial of metronidazole vs. azithromycin for treatment of cyclosporine-induced gingival overgrowth.

Gingival overgrowth usually characterized by increased cellular growth of gingival fibroblasts appears to be multifactorial. In patients receiving CyA for more than 3 months, the incidence can approach 70% and can be attributed to pharmaceutical immunosuppression. Case reports have reported regression of overgrowth with both metronidazole and azithromycin. The goal of this study was to determine the efficacy of metronidazole and azithromycin in reducing CyA-induced gingival overgrowth. Twenty-five patients were included in this double-blinded randomized study. All patients were receiving CyA as medically indicated and diagnosed with gingival overgrowth by a dentist. Patients were randomized to receive either 5-days of azithromycin or 7-days of metronidazole given at baseline only. The extent of gingival overgrowth was measured at 0, 2, 4, 6, 12, and 24 wk. Fourteen patients at CCF and 11 patients at CCHMC were studied. Repeated measures anova was performed to assess differences within and between groups. Gingival overgrowth at baseline was not statistically different between groups. The mean degree of gingival overgrowth after treatment was different across all time intervals (p = 0.0049) showing azithromycin to be more effective than metronidazole. Therapy with azithromycin offers an effective alternative to the management of CyA-induced gingival overgrowth.

Incidence and severity of vesicoureteral reflux in children related to age, gender, race and diagnosis.

PURPOSE: We determine if the incidence and grade of vesicoureteral reflux (VUR) differs in children based on age, race and gender, and if the incidence and severity of VUR are related to race in girls younger than 7 years presenting for evaluation after urinary tract infection (UTI). MATERIALS AND METHODS: The records of all children who underwent a voiding cystourethrogram or radionuclide cystogram between 1993 and 2001 were retrospectively reviewed. Age, gender, race, clinical indication and highest grade of VUR were recorded for the first voiding cystourethrogram or radionuclide cystogram. Frequency tables and logistic regression were conducted to correlate demographics to incidence and severity of VUR. RESULTS: A total of 15,504 patients were included in the analysis. Overall, black children were a third as likely as white children (p <0.0001) and females were twice as likely as males (p <0.0001) to have VUR. Compared to children 0 to 2 years old, the occurrence of reflux was 0.5 times as likely in those 3 to 6 years old (p <0.0001), 0.3 times as likely in those 7 to 11 years old (p <0.0001) and 0.15 times as likely in those 12 to 21 years old (p <0.0001). When analyzing children with UTI, results were similar. Of the patients with VUR 65% were younger than 7 years. The incidence of VUR in black girls younger than 7 years with a diagnosis of UTI was less than 10% compared to white girls, and no black girl had high grade reflux. In young children referred for UTI the incidence and severity of VUR in black patients were significantly lower than those of white girls. CONCLUSIONS: This study validates previous observations regarding the low incidence of VUR in black children.

Epiphyseal stapling and recombinant human growth hormone for correction of genu valgum in children with chronic renal insufficiency.

Genu valgum (GV) and growth retardation are known complications of chronic renal insufficiency (CRI) in children. Physeal stapling is the preferred method for GV correction, provided epiphyseal growth continues after stapling. Growth retardation in these children thus renders this mode of therapy unreliable. The only alternative is corrective osteotomy with the associated risks, such as non-union of bone and recurrence. The authors sought to determine if recombinant human growth hormone (rhGH) administered after stapling can bring about continued physeal growth needed for correction. The medical records of five patients with CRI, GV, and growth retardation who had physeal stapling performed and received rhGH were reviewed. Resolution of GV and improvement in linear height was achieved in four patients within 2 years. The authors conclude that children with CRI, growth retardation, and moderate GV benefit from the simultaneous use of rhGH and knee stapling for correction of GV, thus avoiding osteotomies.

Long versus standard initial steroid therapy for children with the nephrotic syndromeA report from the Southwest Pediatric Nephrology Study Group.

A retrospective cohort study was conducted by the Southwest Pediatric Nephrology Study Group (SPNSG) to address whether a longer initial course of corticosteroids in patients with idiopathic nephrotic syndrome (INS) provides superior protection against relapse without increased adverse effects. In order to be included in the evaluation, patients with INS must have responded to an initial steroid course, either standard or long regimen as defined here, and completed at least 1 year of follow-up. The standard regimen consisted of prednisone 2.0+/-0.3 mg/kg per day or 60+/-10 mg/m(2) per day for 28+/-4 days, followed by alternate-day prednisone for 4-12 weeks. The long regimen consisted of daily prednisone 2.0+/-0.3 mg/kg per day or 60+/-10 mg/m(2) per day for 42+/-6 days, followed by alternate-day prednisone for 6-14 weeks. The primary outcome measure was relapse of NS within 12 months of discontinuing the initial course of prednisone. There were 151 children who met the criteria for the study; 82 received the standard regimen and 69 the long regimen. The two groups did not differ in age, race, blood pressure, serum albumin, or serum cholesterol prior to the initial steroid course. The cumulative prednisone dose was 49% higher in the long regimen group than in the standard regimen group. Relapse within 12 months was reported in 72.5% of patients who received the long regimen versus 84.1% of those who received the standard regimen. The odds ratio for relapse within 12 months was 0.496 (95% confidence interval 0.22, 1.088), long versus standard regimen. This did not reach statistical significance ( chi(2)=3.058, P=0.08). The odds ratio of experiencing at least one side effect was 3.76, long relative to standard regimen ( n=133, P<0.001). Our data suggest that prolongation of the steroid treatment for the initial episode of steroid-sensitive NS may have a beneficial effect, but at the cost of increased side effects. However, definitive conclusions are limited by the retrospective design of the study and the number of patients. This may have caused failure to achieve statistical significance on the basis of a type II error.

Venous pressure monitoring does not accurately predict access failure in children.

Access failure is a significant cause of morbidity and mortality in hemodialysis patients. Routine monitoring of arteriovenous (AV) fistulas and grafts could increase access longevity. Dynamic venous pressure monitoring is a surveillance test advocated to detect early signs of vascular thrombosis. Venous pressure measurements obtained, per DOQI recommendations, in children undergoing hemodialysis with an AV fistula or graft were reviewed. Baseline venous pressures were established by calculating the mean of venous pressures obtained without an antecedent thrombosis. A paired t-test was performed comparing mean baseline pressure measurements with pressures immediately preceding each thrombosis episode. Since some patients had multiple thrombosis episodes, the assumption of independence was not met. A second paired t-test was performed comparing mean baseline pressures with the mean pressure measurement per individual, obtained immediately preceding a thrombosis episode; 335 venous pressures were collected in ten pediatric patients. Eighteen thromboses occurred in five patients, in whom a total of 241 venous pressures were measured. Venous pressures did not correlate with thrombotic events ( P=0.4284). Specific thrombotic events for each patient were correlated with mean patient-specific venous pressures and showed no correlation ( P=0.3229). Dynamic venous pressure monitoring is not an adequate predictor of access thrombosis in pediatric patients.