Cross-Disciplinary Biomarkers Research: Lessons Learned by the CKD Biomarkers Consortium.

Significant advances are needed to improve the diagnosis, prognosis, and management of persons with CKD. Discovery of new biomarkers and improvements in currently available biomarkers for CKD hold great promise to achieve these necessary advances. Interest in identification and evaluation of biomarkers for CKD has increased substantially over the past decade. In 2009, the National Institute of Diabetes and Digestive and Kidney Diseases established the CKD Biomarkers Consortium (http://www.ckdbiomarkersconsortium.org/), a multidisciplinary, collaborative study group located at over a dozen academic medical centers. The main objective of the consortium was to evaluate new biomarkers for purposes related to CKD in established prospective cohorts, including those enriched for CKD. During the first 5 years of the consortium, many insights into collaborative biomarker research were gained that may be useful to other investigators involved in biomarkers research. These lessons learned are outlined in this Special Feature and include a wide range of issues related to biospecimen collection, storage, and retrieval, and the internal and external quality assessment of laboratories that performed the assays. The authors propose that investigations involving biomarker discovery and validation are greatly enhanced by establishing and following explicit quality control metrics, including the use of blind replicate and proficiency samples, by carefully considering the conditions under which specimens are collected, handled, and stored, and by conducting pilot and feasibility studies when there are concerns about the condition of the specimens or the accuracy or reproducibility of the assays.

Glucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome.

The impact of glucocorticoids (GC) on skeletal development has not been established. The objective of this study was to examine changes in volumetric bone mineral density (vBMD) and cortical structure over 1 year in childhood nephrotic syndrome (NS) and to identify associations with concurrent GC exposure and growth. Fifty-six NS participants, aged 5 to 21 years, were enrolled a median of 4.3 (0.5 to 8.1) years after diagnosis. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained at enrollment and 6 and 12 months later. Sex, race, and age-specific Z-scores were generated for trabecular vBMD (TrabBMD-Z), cortical vBMD (CortBMD-Z), and cortical area (CortArea-Z) based on >650 reference participants. CortArea-Z was further adjusted for tibia length-for-age Z-score. Quasi-least squares regression was used to identify determinants of changes in pQCT Z-scores. At enrollment, mean TrabBMD-Z (-0.54 ± 1.32) was significantly lower (p = 0.0001) and CortBMD-Z (0.73 ± 1.16, p < 0.0001) and CortArea-Z (0.27 ± 0.91, p = 0.03) significantly greater in NS versus reference participants, as previously described. Forty-eight (86%) participants were treated with GC over the study interval (median dose 0.29 mg/kg/day). On average, TrabBMD-Z and CortBMD-Z did not change significantly over the study interval; however, CortArea-Z decreased (p = 0.003). Greater GC dose (p < 0.001), lesser increases in tibia length (p < 0.001), and lesser increases in CortArea-Z (p = 0.003) were independently associated with greater increases in CortBMD-Z. Greater increases in tibia length were associated with greater declines in CortArea-Z (p < 0.01); this association was absent in reference participants (interaction p < 0.02). In conclusion, GC therapy was associated with increases in CortBMD-Z, potentially related to suppressed bone formation and greater secondary mineralization. Conversely, greater growth and expansion of CortArea-Z (ie, new bone formation) were associated with declines in CortBMD-Z. Greater linear growth was associated with impaired expansion of cortical area in NS. Studies are needed to determine the fracture implications of these findings.