INDEPENDENT RISK FACTOR FOR CKD PROGRESSION
Metabolic acidosis is both a complication of CKD and a cause of its progression1,4,10,17,20
Increasing serum bicarbonate has been shown to slow CKD progression21-24
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In several, single-center, prospective studies, oral alkali supplementation or reduction of acid production through consumption of a very low protein diet supplemented with ketoanalogs led to reductions in:
- biomarkers of kidney injury and/or net acid excretion22-25
- the rate and extent of eGFR decline21-23,25-27
- the proportion of subjects who experienced rapid decline in eGFR (ie, >3 mL/min/1.73m2)26,27
- progression to a renal endpoint (eg, dialysis, creatinine clearance <10 mL/min, >50% reduction in eGFR)21,26
Metabolic acidosis is associated with an increased risk of CKD progression and risk of mortality19,28-32
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Multiple, large, retrospective cohort analyses have demonstrated that the relationship between decreasing serum bicarbonate levels and clinical outcomes appears to be a continuum: as serum bicarbonate decreases from normal levels, the risk of adverse outcomes like death or progression of CKD progressively increases19,28-32
- Each 1 mEq/L decline below the normal range of serum bicarbonate (22–29 mEq/L) is associated with a 3%–9% increased risk of CKD progression19,28-30
- The association of low serum bicarbonate with progression of kidney disease is independent of baseline eGFR and other clinical, demographic, and socioeconomic factors19,28-30
- The association between metabolic acidosis and increasing risk of mortality in non-dialysis-dependent CKD patients and healthy adults with a range of serum bicarbonate values has been demonstrated after adjusting for kidney disease severity and a wide variety of other comorbid conditions30-32
Metabolic acidosis was shown to be an independent predictor of adverse renal outcomes33
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In a longitudinal analysis in over 51,000 patients with non-dialysis dependent Stage 3-5 CKD:
- The incidence of DD40 (death, dialysis, kidney transplant, or ≥40% eGFR decline) over a 2-year period was significantly higher in patients with chronic metabolic acidosis than in patients with normal serum bicarbonate levels (22–29 mEq/L)
INCIDENCE RATE OF DD40 AT 2 YEARS33
†After controlling for potential confounders.
Download the Reaven et al Poster #FR-PO274, ASN, 2019 for more information about these data
KDIGO guidelines recommend using validated risk prediction tools to evaluate patient risk of progression to kidney failure6
- Based on the work of Dr Navdeep Tangri and colleagues, the 8 variable Kidney Failure Risk Equation (KFRE) predicts the 2-year and 5-year risk of CKD progression to ESRD28
- Serum bicarbonate is one of the 8 variables used in KFRE
- The Neph+® app may be used to calculate patient 2- and 5-year risk of kidney failure as measured by the 8-variable KFRE
- Download Neph+® on the App Store or Google Play
Hear from a Nephrologist
Navdeep Tangri, MD, PhD‡:
What is the role of metabolic acidosis in CKD risk prediction?
‡Dr Tangri is a paid consultant of TRICIDA, Inc.
Continue to the next page to learn more about the underlying pathophysiology and consequences of metabolic acidosis
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Read more
Wesson DE et al (2020):
Mechanisms of metabolic acidosis–induced kidney injury in chronic kidney disease
Go to ARTICLE
Reaven et al Poster #FR-PO274, ASN, 2019:
Metabolic acidosis is an independent predictor of adverse renal outcomes and higher costs in patients with chronic kidney disease
download poster
Goraya N and Wesson DE (2019):
Clinical evidence that treatment of metabolic acidosis slows the progression of chronic kidney disease
Go to ARTICLE