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ADVERSE EFFECTS ON PHYSICAL FUNCTION

Metabolic acidosis may lead to impaired physical function4,6,20,34,35,47

Lower serum bicarbonate levels are associated with reduced lower extremity physical function48

  • Data from the NHANES III study showed that serum bicarbonate below 23 mEq/L was associated with low gait speed and quadricep strength after multivariable adjustment48
  • In addition to limiting one’s activities of daily living, worsening lower extremity function has been shown to be strongly predictive of subsequent risk of mortality among patients with CKD49,50

Correcting metabolic acidosis in CKD improves muscle mass and physical function9,10,26,27,51,52

  • Improvements in muscle mass and physical function observed in clinical studies include:
    • Increased lean body mass measured by dual energy X-ray absorptiometry (DXA) and by anthropometric measurements such as mid-arm muscle circumference26,27,51,52
    • Faster completion of 5-times and 10-times sit-to-stand tests9
    • Improved physical function-related quality of life10

Managing metabolic acidosis may limit loss of bone mineral density34,36,53-56

  • Direct evidence that management of chronic metabolic acidosis improves bone density in patients with CKD has not been demonstrated; however, studies in other clinical populations have shown positive effects on bone when acidosis is corrected with alkali treatment, including:
    • Improved bone histology and increased bone mineral density as measured by dual X-ray absorptiometry in patients with distal renal tubular acidosis53
    • Achievement of normal stature in infants and children with renal tubular acidosis54
    • Lessened negative calcium and phosphorous balance, reduced bone resorption, and increased rate of bone formation in postmenopausal women55,56
    • Slowing of progression of secondary hyperparathyroidism in ESRD patients with high bone turnover and stimulation of bone turnover in ESRD patients with low bone formation34

Serum bicarbonate levels were correlated with the predicted risk of adverse bone and muscle outcomes57

  • In a longitudinal observational analysis of over 51,000 patients with non-dialysis-dependent CKD Stage 3-5 followed for up to 10 years:
    • Patients with metabolic acidosis (12 to <22 mEq/L) at baseline were found to be younger with more co-morbidities and more advanced kidney disease than those with normal serum bicarbonate levels (22–29 mEq/L)

After 2 years, the incidence of fractures and falls and failure to thrive* were significantly higher in patients with metabolic acidosis than patients with normal serum bicarbonate levels (22–29 mEq/L)

*Failure to thrive included muscle and functional outcome.

INCIDENCE OF adverse bone and muscle/functional outcomes at 2 years57

Adverse bone and muscle/functional outcomes at 2 years comparing metabolic acidosis to normal serum bicarbonate.
Increasing serum bicarbonate results in decreased risk of failure to thrive and decreased risk of bone fracture/risk of fall.

Download the Reaven et al Poster #SA-PO836, ASN, 2019 for more information about these data

Correction of metabolic acidosis in CKD patients has beneficial effects on nutritional parameters9,26,51,58-60

  • Protein-energy wasting (PEW) refers to the nutritional and catabolic alterations that occur in CKD and is associated with morbidity and mortality61
  • Metabolic acidosis contributes to PEW by causing skeletal muscle proteolysis, hypoalbuminemia, and negative nitrogen balance61-63
  • Correction of acidosis in CKD patients has demonstrated beneficial effects on nutritional parameters, including9,26,51,58-60:
    • protein catabolism
    • protein turnover
    • serum albumin
    • nitrogen balance
    • subjective global assessment for nutritional status score

Hear from a Patient

Sharon, patient with CKD:

Opinions reflected in the above patient video are those of the patient. CKD is complex and patient symptoms may vary.

Read More

Reaven et al Poster #SA-PO836, ASN, 2019:
Metabolic acidosis is associated with failure to thrive and fractures/falls in patients with chronic kidney disease
download poster
Abramowitz MK (2014):
Acid-base balance and physical function
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