Farah N. Ali

Heritability and Environmental Factors Affecting Vitamin D Status in Rural Chinese Adolescent Twins

CONTEXT Factors associated with the high prevalence of vitamin D deficiency in China are not well described, especially among Chinese adolescents. OBJECTIVES The aim of the study was to examine important environmental or sociodemographic factors influencing 25-hydroxyvitamin D [25(OH)D] levels and estimate its heritability. DESIGN A sample of 226 male and female adolescent twins aged 13-20 yr from a large prospective twin cohort of rural Chinese children and adolescents that has been followed for 6 yr were evaluated. MAIN OUTCOME MEASURE(S) Blood level of 25(OH)D was measured using tandem mass spectrometry methodology. RESULTS The overall mean (SD) 25(OH)D level was 18.0 (9.4) ng/ml, with wide variation by gender and season. In males (47.4% of subjects), the mean (SD) 25(OH)D level was 12.1 (4.2) ng/ml in non-summer and 27.4 (8.8) ng/ml in summer; in females, it was 10.1 (4.1) ng/ml in non-summer and 19.5 (6.3) ng/ml in summer. A multivariate model that included gender, age, season, physical activity, and student status demonstrated that male gender, summer season, and high physical activity significantly increased 25(OH)D levels. Summer season and male gender also significantly decreased the risk of being in the lowest 25(OH)D tertile. Overall, 68.9% of the variability in 25(OH)D level was attributable to additive genetic influence. Stratification by gender found that in males, 85.9% of the variability in 25(OH)D level was attributable to such influence, but in females, it was only 17%. CONCLUSION In this sample of rural Chinese adolescents, 25(OH)D level was influenced by gender, season, and physical activity level. There was a strong genetic influence on 25(OH)D level in males only.

Vitamin D Deficiency in Children With Chronic Kidney Disease: Uncovering an Epidemic

BACKGROUND. Vitamin D deficiency in children adversely affects bone development by reducing mineralization. Children with chronic kidney disease are at risk for altered bone development from renal osteodystrophy and concomitant vitamin D deficiency. The pediatric Kidney Disease Outcomes Quality Initiative guidelines suggest measuring serum 25-hydroxyvitamin D (25[OH]D) levels if serum parathyroid hormone levels are above the target range for chronic kidney disease stages 2 and beyond, but the magnitude of vitamin D deficiency in children with chronic kidney disease is not well studied. OBJECTIVES. The purpose of this work was to determine whether children with chronic kidney disease had vitamin D deficiency, to evaluate whether the prevalence of vitamin D deficiency changed over time, and to examine seasonal and ethnic differences in 25(OH)D levels. METHODS. 25(OH)D levels in children with chronic kidney disease (stages 1–5) were measured over a 10-year period from 1987 to 1996. Data were also collected for a contemporary group of patients from 2005 to 2006. RESULTS. The prevalence of vitamin D deficiency ranged from 20% to 75% in the decade studied. There was a significant trend for decreasing 25(OH)D levels over the decade, both at the group and individual levels. Seasonal variation was noted. In our contemporary population with chronic kidney disease, the mean 25(OH)D level was 21.8 ng/mL; we found a prevalence of vitamin D deficiency of 39%. Black and Hispanic patients had lower levels of 25(OH)D than white patients. CONCLUSIONS. Children with chronic kidney disease have great risk for vitamin D deficiency, and its prevalence was increasing yearly in the studied decade. Contemporary data show that vitamin D deficiency remains a problem in these children. Sunlight exposure and ethnicity play a role in levels of 25(OH)D. Our data support the recent pediatric Kidney Disease Outcomes Quality Initiative guidelines for measurement of 25(OH)D levels in children with chronic kidney disease and secondary hyperparathyroidism.

Thrombotic Microangiopathy and Peritubular Capillary C4d Expression in Renal Allograft Biopsies

BACKGROUND AND OBJECTIVES This study characterizes the pathologic and clinical relationships of thrombotic microangiopathy (TMA) to antibody-mediated rejection (AMR) in renal allograft biopsies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Consecutive renal allograft biopsies, routinely stained for C4d over a period of 51 months (n=1101), were reviewed. For comparative analysis of histology and clinical features, additional patients with TMA and peritubular capillary (PTC) C4d (n=5) were combined with those identified in the 51-month period of review (n=6). RESULTS One hundred eighty-two of 1073 adequate biopsies from 563 allografts had PTC C4d in the study period. Six of 37 biopsies with TMA had PTC C4d (five at ≤90 days and one at 213 days). Early (≤90 days) C4d+ biopsies (n=5) had more frequent TMA (11.9% C4d+ versus 3.4% C4d-; odds ratio, 3.84; P=0.03). Graft loss was significantly greater in an early C4d+TMA+ group (n=5 study+2 archival patients) than in C4d+ controls without TMA (n=21) (57% versus 9.5%; P=0.02). Early TMA+C4d+ biopsies had more severe glomerulopathy and less severe arteriolopathy than TMA+C4d- and had more frequent neutrophilic capillaritis than TMA-C4d+ biopsies. CONCLUSIONS TMA was infrequent in this series of unselected, consecutive, renal allograft biopsies (3.4%). PTC C4d may be a significant risk factor for early TMA, and TMA is associated with glomerular thrombi and neutrophilic capillaritis. TMA in allografts with suspected AMR may portend a higher risk of graft loss.

Native BK viral nephropathy in a pediatric heart transplant recipient

Ali FN, Meehan SM, Pahl E, Cohn RA. Native BK viral nephropathy in a pediatric heart transplant recipient.
Pediatr Transplantation 2010: 14:E38–E41.

Treatment of childhood nephrotic syndrome with long-term, low-dose tacrolimus.

AIM Children with steroidresistant (SR) and steroid-dependent (SD) nephrotic syndrome (NS) pose a treatment challenge. Literature on the use of tacrolimus (TAC), a calcineurin inhibitor, for maintenance treatment of NS is sparse. We aimed to evaluate the efficacy and safety of low-dose, long-term TAC for inducing and sustaining remission in children with SD/SR NS. METHODS Data from patients treated at our center from 1999 to 2009 were analyzed. RESULTS 40 patients with NS were treated with TAC for 3 - 80-month periods (median 25.2 months). Diagnoses included focal segmental glomerulosclerosis (FSGS) (60%), IgM nephropathy (15%), minimal change disease (20%) and membrano-proliferative glomerulonephritis (MPGN) (5%). 58% of patients had been previously treated with alternate agents. After 1, 2, and 3 years on TAC, complete remission was achieved in 26%, 48%, and 29% of patients; complete or partial remission was achieved in 85%, 100%, and 86%, respectively (p < 0.05). Median time to remission was 41 days (range: 10 - 270 days). FSGS and SR diseases were associated with lower likelihood of remission (p < 0.05). Remission was equally likely in both treatment naïve patients and those who had received prior second-line agents. CONCLUSION Our results demonstrate that TAC treatment for children with SR/SD NS is associated with high rates of sustained remission, even when prior second-line agents failed.

Cord Blood Ferritin and Fibroblast Growth Factor-23 Levels in Neonates.

CONTEXT Elevated levels of the phosphate-regulating hormone, fibroblast growth factor-23 (FGF-23) are associated with skeletal and cardiovascular disease. Levels of FGF-23 are elevated in neonates, but the mechanisms are poorly understood. Iron deficiency is a recently described stimulus for FGF-23 production. OBJECTIVE To test the hypothesis that lower fetal iron status, as measured by lower cord blood ferritin, is independently associated with elevated FGF-23 levels in neonates. DESIGN AND PARTICIPANTS This is a cross-sectional study of 64 full-term, healthy neonates. SETTING This study took place in a university-based, tertiary care center. MAIN OUTCOME MEASURES Plasma levels of second generation C-terminal FGF-23 (cFGF-23) and intact FGF-23 (iFGF-23). RESULTS Levels of cFGF-23 ranged from 108 to 7508 reference units (RU)/ml (median, 824 RU/ml), and iFGF-23 from undetectable (<8.5) to 135.4 pg/ml (median, <8.5 pg/mL). Ferritin ranged from 58 to 719 ng/ml (mean, 203 ng/ml). Lower cord blood ferritin levels were associated with higher cFGF-23 (r = −0.320; P = .014), but not iFGF-23 levels (r = −0.222; P = .082). In multivariate analyses adjusted for glycemic indices, maternal race, and parity, lower ferritin levels remained independently associated with higher cFGF-23 levels (B = −0.261, P = .01). In the full models, higher cord blood glucose and C-peptide levels were also independently associated with higher cFGF-23 levels. CONCLUSIONS cFGF-23, but not iFGF-23 levels, are elevated in cord blood of healthy term neonates and independently associated with lower serum ferritin and higher glycemic indices.

Obstructive uropathy is associated with polyomavirus viremia in pediatric kidney transplantation.

Matossian D, Langman CB, Cohn RA, Ali FN. Obstructive uropathy is associated with polyomavirus viremia in pediatric kidney transplantation.

Hemofiltration circuit use beyond 72 hours in pediatric continuous renal replacement therapy

Introduction During continuous renal replacement therapy (CRRT), hemofiltration circuits ideally are changed after 72 h since tubing integrity and flow rates are not guaranteed after this time interval. This potential risk must be weighed against the risk of hypotension during elective circuit changes in the unstable patient. The aim of this study was to examine the safety of circuits used beyond 72 h in pediatric CRRT. Methods A retrospective chart review of all patients who underwent CRRT at our institution from January 2003 to October 2005 was performed. Procedures were divided into standard (≤72 h) and extended (>72 h) circuit duration groups. Patients who had more than one CRRT procedure (n=13) were excluded from study. Results 71 CRRT procedures were performed for 71 patients. A total of 254 circuits were used, of which 64 (25%) were used for >72 h. For circuits >72 h, the mean duration of use was 5.5 days ± 1.8 (range 4–11). There were no differences between the groups in age (p=0.12), weight (p=0.48), diagnosis (p=0.21), CRRT indication (p=0.07), CRRT mode (p=0.37), anticoagulation (p=0.53), blood flow rate (p=0.06), replacement rate (p=0.50) or dialysate rate (p=0.89). There were no incidents of membrane or tubing rupture in either group. Conclusions Use of hemofiltration circuits beyond 72 h may be safe in pediatric patients undergoing CRRT without increased risk of tubing rupture. Our data suggest a need to redefine the limits of prolonged circuit use in pediatric CRRT.