Parathyroid hormone and growth in chronic kidney disease

Abstract

Growth failure is common in children with chronic kidney disease, and successful treatment is a major challenge in the management of these children. The aetiology is multi-factorial with "chronic kidney disease-metabolic bone disorder" being a key component that is particularly difficult to manage. Parathyroid hormone is at the centre of this mineral imbalance, consequent skeletal disease and, ultimately, growth failure. When other aetiologies are treated, good growth can be achieved throughout the course of the disease when parathyroid hormone (PTH) levels are in the normal range or slightly elevated. A direct correlation between PTH levels and growth has not been convincingly established, and the direct effect of PTH on growth has not been adequately described; furthermore, direct actions of PTH on the growth plate are unproven. The effects of PTH on growth stem from the pivotal role that PTH plays in the development of renal osteodystrophy. In severe secondary hyperparathyroidism, the growth plate is altered and growth is affected. At the other end of the spectrum, with an over-suppressed parathyroid gland, the rate of bone turnover and remodelling is markedly diminished, and some data suggest this is associated with poor growth. Most of the data available suggests that avoiding the development of significant bone disease through the strict control of PTH levels permits good growth. Absolute optimal ranges for PTH that maximise growth or minimise growth failure are not yet established.

Medication Adherence and Growth in Children with CKD

“…However, limited research has been conducted to formally assess the magnitude of the effect that interventions to correct these comorbidities have on growth. In the available studies, serum phosphorous, calcium, albumin, and parathyroid hormone levels were poor predictors of short stature (32)(33)(34)(35)(36). Thus, it is possible that some of the current treatment strategies are ineffective in improving growth or that self-reported nonadherence does not necessarily identify a substantial enough degree of medication nonadherence to affect growth.…”

Clinical Practice Guideline for the Management of Chronic Kidney Disease‐Mineral and Bone Disorder

“…The KDOQI guideline proposes a target PTH level of 1.7 × ULN of the reference range (70–110 pg/mL) for children with CKD stage 4, whereas the European EPDWG guideline does not define any target level. With several reports showing that growth retardation does not occur at a PTH level of <2 × ULN ; we consider it reasonable, for this guideline, to control PTH level at ≤1.5 × ULN (100 pg/mL as intact PTH) for children with CKD stage 4.…”

“…A consensus has not been established regarding the recommended target range of PTH for children with CDK stage 5 or 5D , with the KDOQI guidelines proposing 200–300 pg/mL (350), the EPDWG guideline proposing 120–180 pg/mL , and the KDIGO guideline proposing 120–500 pg/mL . A recent international observational study of pediatric peritoneal dialysis patients showed a significantly increased prevalence of clinical symptoms or radiological CKD‐MBD lesions in patients with a PTH level of ≥300 pg/mL and profound growth retardation in patients with a PTH level of ≥500 pg/mL, while a PTH level of <100 pg/mL was associated with a high incidence of low‐turnover bone diseases.…”

Summary of Expert Opinion on the Management of Children With Chronic Kidney Disease and Growth Failure With Human Growth Hormone

“…In the treatment of other non-renal diseases, satisfactory growth can be achieved when PTH levels are within the normal range or slightly higher. Despite the relationship between longitudinal growth and serum PTH levels remains unclear, available data suggest that avoiding the development of a significant bone disease through an adequate control of PTH levels may improve linear growth by a small increase of height SDS (0,09 SD per year) (30).…”

“…Chronic Kidney Disease (CKD) in pediatric and adult patients is characterized by a progressive decline in kidney function, classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) in a system based primarily on glomerular filtration rate (eGFR, ml/min/1.73 m 2 ) and on proteinuria (1). The classification consists of 5 stages based on a decreasing of eGFR: G1 normal or high (≥ 90); G2 mildly decreased (60-89); G3a mildly to moderately decreased (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59); G3b moderately to severely decreased (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44); G4 severely decreased (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) and G5 kidney failure (≤ 15, or dialysis) (1). According to these Guidelines, CKD should be established based on kidney function and damage expressed as eGFR, irrespective of...…”