Longitudinal Associations between Low Serum Bicarbonate and Linear Growth in Children with CKD

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Abstract

Background

Poor linear growth is a consequence of chronic kidney disease (CKD) that has been linked to adverse outcomes. Metabolic acidosis (MA) has been identified as a risk factor for growth failure. We investigated the longitudinal relationship between MA and linear growth in children with CKD and examined whether treatment of MA modified linear growth.

Methods

To describe longitudinal associations between MA and linear growth, we used serum bicarbonate levels, height measurements, and standard deviation (z scores) of children enrolled in the prospective cohort study Chronic Kidney Disease in Children. Analyses were adjusted for covariates recognized as correlating with poor growth, including demographic characteristics, glomerular filtration rate (GFR), proteinuria, calcium, phosphate, parathyroid hormone, and CKD duration. CKD diagnoses were analyzed by disease categories, nonglomerular or glomerular.

Results

The study population included 1082 children with CKD: 808 with nonglomerular etiologies and 274 with glomerular etiologies. Baseline serum bicarbonate levels ≤22 mEq/L were associated with worse height z scores in all children. Longitudinally, serum bicarbonate levels ≤18 and 19–22 mEq/L were associated with worse height z scores in children with nonglomerular CKD causes, with adjusted mean values of –0.39 (95% CI, –0.58 to –0.2) and –0.17 (95% CI, –0.28 to –0.05), respectively. Children with nonglomerular disease and more severe GFR impairment had a higher risk for worse height z score. A significant association was not found in children with glomerular diseases. We also investigated the potential effect of treatment of MA on height in children with a history of alkali therapy use, finding that only persistent users had a significant positive association between their height z score and higher serum bicarbonate levels.

Conclusions

We observed a longitudinal association between MA and lower height z score. Additionally, persistent alkali therapy use was associated with better height z scores. Future clinical trials of alkali therapy need to evaluate this relationship prospectively.

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Most cited references 30

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Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy.

Ashutosh Mahajan, Jan Simoni, Simon Sheather … (2010)

In most patients with hypertensive nephropathy and low glomerular filtration rate (GFR), the kidney function progressively declines despite the adequate control of the hypertension with angiotensin-converting enzyme inhibition. Previously we found that 2 years of oral sodium citrate slowed GFR decline in patients whose estimated GFR (eGFR) was very low (mean 33 ml/min). This treatment also slowed GFR decline in an animal model of surgically reduced nephron mass. Here, we tested if daily oral sodium bicarbonate slowed GFR decline in patients with hypertensive nephropathy with reduced but relatively preserved eGFR (mean 75 ml/min) in a 5-year, prospective, randomized, placebo-controlled, and blinded interventional study. Patients matched for age, ethnicity, albuminuria, and eGFR received daily placebo or equimolar sodium chloride or bicarbonate while maintaining antihypertensive regimens (including angiotensin-converting enzyme inhibition) aiming for their recommended blood pressure targets. After 5 years, the rate of eGFR decline, estimated using plasma cystatin C, was slower and eGFR was higher in patients given sodium bicarbonate than in those given placebo or sodium chloride. Thus, our study shows that in hypertensive nephropathy, daily sodium bicarbonate is an effective kidney protective adjunct to blood pressure control along with angiotensin-converting enzyme inhibition.

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Design and methods of the Chronic Kidney Disease in Children (CKiD) prospective cohort study.

B A Warady, Craig Wong, Frederick Kaskel … (2006)

An estimated 650,000 Americans will have ESRD by 2010. Young adults with kidney failure often develop progressive chronic kidney disease (CKD) in childhood and adolescence. The Chronic Kidney Disease in Children (CKiD) prospective cohort study of 540 children aged 1 to 16 yr and have estimated GFR between 30 and 75 ml/min per 1.73 m2 was established to identify novel risk factors for CKD progression; the impact of kidney function decline on growth, cognition, and behavior; and the evolution of cardiovascular disease risk factors. Annually, a physical examination documenting height, weight, Tanner stage, and standardized BP is conducted, and cognitive function, quality of life, nutritional, and behavioral questionnaires are completed by the parent or the child. Samples of serum, plasma, urine, hair, and fingernail clippings are stored in biosamples and genetics repositories. GFR is measured annually for 2 yr, then every other year using iohexol, HPLC creatinine, and cystatin C. Using age, gender, and serial measurements of Tanner stage, height, and creatinine, compared with iohexol GFR, a formula to estimate GFR that will improve on traditional pediatric GFR estimating equations when applied longitudinally is expected to be developed. Every other year, echocardiography and ambulatory BP monitoring will assess risk for cardiovascular disease. The primary outcome is the rate of decline of GFR. The CKiD study will be the largest North American multicenter study of pediatric CKD.