Pediatric Advances

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Advances in Pediatric Nephrology

Chronic Kidney Disease: Chronicling the Toll on Bone Health

Bone mineral disorders and other metabolic bone abnormalities are among the many adverse effects of chronic kidney disease (CKD) in children. However, few, if any studies are available that provide evidence-based guidelines for assessment and long-term management of CKD-mineral bone disorder.

Dr. Juhi Kumar

To help address this gap in clinical knowledge, pediatric nephrologist Juhi Kumar, MD, MPH, Medical Director of the Pediatric Kidney Transplant Program at NewYork-Presbyterian Komansky Children's Hospital, has led and engaged in a number of studies to better understand the causes of bone abnormalities and potential strategies to minimize their consequences.  CKD-mineral bone disorder is a systemic condition causing abnormalities in calcium, phosphorus, parathyroid hormone, and vitamin D metabolism, as well as in bone turnover, mineralization, and volume. The resulting complications can carry significant morbidity.

In a review article, published in the September 2021 issue of Seminars in Nephrology, Dr. Kumar cites multiple studies that reinforce the need for a greater focus on the long-term effects of CKD on skeletal integrity and growth.

Dr. Kumar emphasizes the need for comprehensive research in bone and mineral metabolism in children with CKD and the establishment of data that can drive the development of evidence-based management strategies.

The detailed paper encompasses several key concerns faced by pediatric nephrologists caring for children whose kidney disease can impact not only their skeletal system, but also place them at higher risk for cardiovascular disease and compromised neurodevelopmental growth. In addition, the article highlights newer data from the NIH’s Chronic Kidney Disease in Children (CKiD) study, which is advancing understanding of the disease, common morbidities and associated risk factors, and disease progression. Among the issues addressed by the review article are:

Evaluating Renal Osteodystrophy

The ideal approach to assessing bone morphology associated with CKD, referred to as renal osteodystrophy, is bone histomorphometry. However, in pediatric CKD, the lack of bone biopsy data and validated radiologic methods have made it challenging to achieve a definitive evaluation and optimal management of bone disorders in these children.

Radiology Studies

Newer imaging modalities are available to assess bone mineral density more thoroughly, including the capability of predicting incident fractures. The conventional bone imaging modalities of X-ray and dual-energy X-ray absorptiometry have shown limited utility for measuring bone mineral density. However, peripheral quantitative computed tomography has demonstrated an advantage over these methods by being able to distinguish cortical from trabecular compartments and by providing bone volumetric and density data. Studies have shown that magnetic resonance imaging and high-resolution MRI may provide data equivalent to bone biopsy in terms of cortical thinning, trabecular architecture, and bone volume.

Biological Markers

The pathophysiology of renal bone disease continues to be a major focus of research, but with inconclusive results. While a single biomarker by itself or in combination with other biomarkers have not yet been identified to accurately diagnose bone mineralization or turnover defects, parathyroid hormone levels appear to be a predictor of high turnover bone disease and poor mineralization.

This research builds on an earlier multicenter study led by Dr. Kumar that focused on 25-hydroxyvitamin D (25OHD) deficiency in children enrolled in the CKiD study. The research team’s analysis of markers of mineral metabolism revealed a 28 percent prevalence of 25OHD deficiency at enrollment. They sought to determine risk factors for 250HD deficiency, including demographic, dietary, and CKD-specific risk factors in children with mild to moderate CKD. Their findings demonstrated that deficiency of 25OHD was predicted by non-white race, inadequate milk intake, absence of nutritional vitamin D supplementation, higher BMI, winter season of blood draw, and proteinuria. A low 250HD level was also a risk factor for low 1,25 dihydroxy vitamin D level and secondary hyperparathyroidism in children with chronic kidney disease.

Dr. Kumar emphasizes the need for comprehensive research in bone and mineral metabolism in children with CKD and the establishment of data that can drive the development of evidence-based management strategies.

Read More

Adverse Consequences of Chronic Kidney Disease on Bone Health in Children. Kumar J, Perwad F. Seminars in Nephrology. 2021 Sep;41(5):439-445.

Prevalence and correlates of 25-hydroxyvitamin D deficiency in the Chronic Kidney Disease in Children (CKiD) cohort. Kumar J, McDermott K, Abraham AG, Friedman LA, Johnson VL, Kaskel FJ, Furth SL, Warady BA, Portale AA, Melamed ML. Pediatric Nephrology. 2016 Jan;31(1):121-9.

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