Intended for US healthcare professionals only.

Register for Updates

About Metabolic Acidosis

Metabolic acidosis in CKD is caused by the kidney’s reduced ability to excrete acid1

Acid-base balance is essential for proper functioning of organs, tissues, and cells2

  • To maintain physiologic blood pH (7.35–7.46), excess acid is removed via the lungs (CO2, a volatile acid) and kidneys (nonvolatile acids)2
    • Adults typically produce between 50 and 75 mEq of nonvolatile acid each day through metabolic processes and the digestion of food, especially animal protein2,3
    • In patients with CKD, the decreased ability of the diseased kidney to excrete nonvolatile acids results in acid accumulation3,4
  • Prior to excretion via the kidney, nonvolatile acids must be buffered1
    • The primary extracellular buffer is bicarbonate (HCO3-)2
    • Intracellular buffers include phosphates and carbonates in bone and anionic proteins in muscle2
    • As CKD advances, the kidney’s capacity to excrete acid is further reduced to the extent that buffering systems are overwhelmed and serum bicarbonate falls below the normal range (22–29 mEq/L)1

Metabolic acidosis is diagnosed by the level of bicarbonate in the blood1

Arrow showing the levels of bicarbonate in the blood

Serum bicarbonate levels determine severity of acidosis

  • The measurement of serum bicarbonate is part of a standard metabolic panel5
  • The normal range for serum bicarbonate is between 22 and 29 mEq/L6
  • Chronic metabolic acidosis is defined as a persistent bicarbonate level below 22 mEq/L in the absence of lung disease1
  • Metabolic acidosis is more prevalent at the later, more severe stages of CKD where there is increased kidney impairment1,7

Metabolic acidosis is common, but often under-recognized*1,8-10

  • It is estimated that 37 million people in the United States—or 15% of the total adult population—are afflicted with CKD, according to the Centers for Disease Control and Prevention11
  • The prevalence and severity of metabolic acidosis in people with CKD progressively increases as kidney function declines. Estimates of the prevalence of metabolic acidosis increase by stage of CKD1,7,11-14:
    • 9.4% of Stage 3a CKD patients
    • 18.1% of Stage 3b CKD patients
    • 31.5% of Stage 4 and 5 CKD patients
Pie chart depicting the different stages of chronic kidney disease (CKD) and the estimated number of adults with metabolic acidosis within the CKD stages. CKD Stage 3a approx. 1.4 Million Metabolic Acidosis Patients. CKD Stage 3b approx. 1.1 Million Metabolic Acidosis Patients. CKD Stage 4 & Stage 5 (non-dialysis) > 600 Thousand Metabolic Acidosis Patients. Pie chart depicting the different stages of chronic kidney disease (CKD) and the estimated number of adults with metabolic acidosis within the CKD stages. CKD Stage 3a approx. 1.4 Million Metabolic Acidosis Patients. CKD Stage 3b approx. 1.1 Million Metabolic Acidosis Patients. CKD Stage 4 & Stage 5 (non-dialysis) > 600 Thousand Metabolic Acidosis Patients.

*Defined as underdiagnosed and/or undertreated.

Data on file. NHANES 1999-2004 reports prevalence of CKD Stages 3 and 4 for the US adult population ages 20 and older. CKD Stage 3 and 4 prevalence was calculated using NHANES prevalence and 2016 US Census data. Stage 3a (70%) and 3b (30%) were approximated using NCCD-CDC Surveillance System; Stage 5 non-dialysis included based on Inker et al grouping of Stage 4 & 5 prevalence rate. Metabolic acidosis prevalence by Stage 3a, 3b, 4, and 5 reported by Inker et al (2011).

Approximately 3 million CKD patients in the US have metabolic acidosis, but roughly one-third are diagnosed8,11,14,15

  • While KDIGO and KDOQI guidelines recommend maintaining serum bicarbonate within normal range (22–29 mEq/L), current management options like oral alkali supplementation and dietary modification are limited6,16,17
    • CKD patients commonly have sodium-sensitive comorbidities—such as poorly controlled hypertension, cardiovascular disease, congestive heart failure, and edema—which may further limit the use of current management options17
  • There are currently no FDA-approved options for the management of chronic metabolic acidosis

Metabolic acidosis is underdiagnosed and undertreated in patients with CKD18,19

  • An analysis of claims and prescription data from a cohort of over 80,000 patients with laboratory data indicative of unequivocal Stage 3-5 CKD and chronic metabolic acidosis showed18:
    • Metabolic acidosis was diagnosed in 20.9% of the cohort and treated in 15.3% of the cohort

Metabolic acidosis is underdiagnosed18

Bar graph showing the percentage of diagnosed metabolic acidosis compared to undiagnosed metabolic acidosis.

Metabolic acidosis is undertreated18

Bar graph showing the percentage of treated metabolic acidosis compared to untreated metabolic acidosis.

These graphics were adapted from Tangri N. Metabolic acidosis is underdiagnosed and undertreated in patients with chronic kidney disease. Poster presented at: American Society of Nephrology Kidney Week 2019; November 5-10, 2019; Washington, DC.

  • The low percentage of patients treated was similar to data from the CRIC (Chronic Renal Insufficiency Cohort) study, an earlier longitudinal study of over 1000 patients with Stage 2-4 CKD and metabolic acidosis (serum bicarbonate <22 mEq/L)19
    • Less than 3% of the cohort were treated with oral alkali therapy

Treatment of metabolic acidosis is a critical unmet need18,19

Bar graph showing the proportion of patients with metabolic acidosis receiving treatment as reported by Dobre (2013) and Tangri (2019)

Download the Tangri Poster #FR-PO632, ASN, 2019 for more information about these data

Hear from a Nephrologist

Navdeep Tangri, MD, PhD:

Metabolic acidosis is underdiagnosed and undertreated in patients with CKD

‡Dr Tangri is a paid consultant of TRICIDA, Inc.

Download Dr Tangri's presentation featured in this video

Continue to the next page to learn more about metabolic acidosis as an independent risk factor for CKD progression

Next Page

Read More

Tangri Poster #FR-PO632, ASN, 2019:
Metabolic acidosis is underdiagnosed and undertreated in patients with chronic kidney disease
download poster
Inker LA et al (2011):
Estimated GFR, albuminuria, and complications of chronic kidney disease
Go to Article
Kidney Disease Improving Global Outcomes® (2012):
KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease
Access the Guidelines
National Kidney Foundation-Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines (2002):
NKF-KDOQI Clinical Practice Guidelines for chronic kidney disease evaluation, classification, and stratification
ACCESS THE GUIDELINES