Acid Base Balance and Progression of Kidney Disease
Section snippets
Mechanism of Maintaining Acid-Base Balance
Tight regulation of acid-base balance plays a pivotal role in normal human physiology. Substantial changes in intracellular and extracellular pH are not compatible with life. Human beings have multiple mechanisms in place to protect against extracellular acidemia and alkalemia. The three major regulators of acid-base balance are as follows: excretion of carbon dioxide via the lungs, intracellular and extracellular buffering systems, and renal elimination of nonvolatile acid and generation of
CLINICAL ACID-BASE PARAMETERS IN CKD
The National Kidney Foundation Kidney Disease Outcomes Quality Initiative Guidelines suggest treating metabolic acidosis and maintaining bicarbonate level at 22 mEq/L or greater.36 Use of serum bicarbonate as a treatment target oversimplifies the disease process and treatment of metabolic acidosis in patients with CKD. Besides bicarbonate concentration, dietary acid load, renal acid excretion, and net acid balance also are significant parameters involved in metabolic acidosis (Table 1).
Dietary
Low Bicarbonate Concentration and CKD Progression
Low bicarbonate concentrations were shown to be associated with faster CKD progression in multiple epidemiologic studies (Table 2). Overall, with every 1 mEq/L increase in bicarbonate concentration, the risk of CKD progression (defined as either end-stage renal disease [ESRD] or a 50% reduction in GFR) decreased by 3% to 8% in approximately 4 years.47, 48, 49 In the Chronic Renal Insufficient cohort (CRIC), which includes non-institutionalized partipants with CKD, participants with CKD stages 2
INTERVENTIONAL STUDIES ON THE EFFECT OF ALKALI THERAPY ON CKD PROGRESSION
Several interventional studies investigated the effect of alkali therapy on CKD progression. We have identified seven main studies and summarized the findings in Table 4.21, 5759, 60, 61, 62, 63 The findings from these studies suggest that alkali therapy using either sodium bicarbonate/citrate or fruits and vegetables has promising effects on preserving renal function. However, most of these studies were conducted in hypertensive patients with either normal to mildly low bicarbonate levels.
Ongoing Clinical Trials on Alkali Therapy and CKD Progression
There are several ongoing clinical trials examining the effect of sodium bicarbonate supplementation in CKD, and they have been described previously.5, 31 Two of these trials examine CKD progression as the primary outcome. One clinical trial is based in Italy (ClinicalTrials.gov; NCT01640119) and is a multicenter, randomized controlled, open-label study.66 The investigators plan to randomize 728 patients with CKD stages 3b to 4 to either bicarbonate groups (with administration of sodium
SUMMARY
A large body of work in animals and human beings supports the hypothesis that metabolic acidosis has a deleterious effect on the progression of kidney disease. Alkali therapy, whether pharmacologically or through dietary intervention, appears to slow CKD progression, but a larger randomized controlled trial with a low risk of bias is required to reach a more definitive conclusion. Recent work on urinary ammonium excretion has shown that the development of prognostic tools related to acidosis is
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Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy
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Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate
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Cited by (20)
Eubicarbonatemic Hydrogen Ion Retention and CKD Progression
2021, Kidney MedicineCitation Excerpt :Age, largely through the associated kidney function decline, and dietary H+ load codetermine the small but significant decreases in serum [HCO3ˉ] and blood pH that characterize this life stage evidencing H+ retention.59 Trials on the role of H+ retention in CKD progression have largely examined hypobicarbonatemic metabolic acidosis in patients with CKD 3-5.23-29 Only a single small study has tested the impact of alkali (0.5 mEq/kg of lean body weight) in patients with CKD 2 with subclinical metabolic acidosis yielding a positive outcome at 5 and 10 years of follow-up (Table 1).8,42
Nephrolithiasis and Elevated Urinary Ammonium: A Matched Comparative Study
2020, UrologyCitation Excerpt :Due to our study design, we were not able to further investigate this link, though further research may be useful in identifying potential sex-specific cutoffs. Chronic kidney disease has also been found to decrease ammonia excretion thus leading to metabolic acidosis16-18 however we did not detect any differences between the 2 groups in comparing their creatinine or estimated glomerular filtration rate. Other factors associated with elevated urinary ammonium included recent positive urine culture with urease producing organisms and recurrent UTIs.
Metabolic acidosis in chronic kidney disease: mere consequence or also culprit?
2024, Pflugers Archiv European Journal of PhysiologyMetabolic acidosis in pediatric kidney transplant recipients
2023, Pediatric NephrologyOlder patients are less prone to fast decline of renal function: a propensity-matched study
2023, International Urology and Nephrology
Financial disclosure: supported by K23 DK114476 from the National Institutes of Health and an American Society of Nephrology Carl W. Gottschalk Research Scholar Grant (W.C.); and by K23 DK099438 and R03 DK116023 from the National Institutes of Health (M.K.A.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflict of interest statement: Matthew Abramowitz has consulted for Tricida, Inc.