Review
Metabolic Acidosis of CKD: Diagnosis, Clinical Characteristics, and Treatment

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Metabolic acidosis is noted in the majority of patients with chronic kidney disease (CKD) when glomerular filtration rate (GFR) decreases to less than 20% to 25% of normal, although as many as 20% of individuals can have acid-base parameters close to or within the normal range. Acidosis generally is mild to moderate in degree, with plasma bicarbonate concentrations ranging from 12 to 22 mEq/L (mmol/L), and it is rare to see values less than 12 mEq/L (mmol/L) in the absence of an increased acid load. Degree of acidosis approximately correlates with severity of renal failure and usually is more severe at a lower GFR. The metabolic acidosis can be of the high-anion-gap variety, although anion gap can be normal or only moderately increased even with stage 4 to 5 CKD. Several adverse consequences have been associated with metabolic acidosis, including muscle wasting, bone disease, impaired growth, abnormalities in growth hormone and thyroid hormone secretion, impaired insulin sensitivity, progression of renal failure, and exacerbation of β2-microglobulin accumulation. Administration of base aimed at normalization of plasma bicarbonate concentration might be associated with certain complications, such as volume overload, exacerbation of hypertension, and facilitation of vascular calcifications. Whether normalization of plasma bicarbonate concentrations in all patients is desirable therefore requires additional study. In the present review, we describe clinical and laboratory characteristics of metabolic acidosis, discuss potential adverse effects, and address benefits and complications of therapy.

Section snippets

Prevalence of metabolic acidosis in patients with CKD

The exact prevalence of metabolic acidosis in patients with CKD is unknown. Early studies indicated that hypobicarbonatemia caused by metabolic acidosis only developed when GFR decreased to less than 25% of normal.3 The recent analysis of the third annual National Health and Nutrition Examination Survey (NHANES III; 1988 to 1994)16 found that a detectable decrease in plasma bicarbonate concentration was not seen until GFR was less than 20 mL/min (<0.33 mL/s). Based on estimates of the number of

Onset, Severity, and Stability of Metabolic Acidosis

Clinical characteristics of metabolic acidosis in patients with CKD are listed in Table 1. A detectable decrease in plasma bicarbonate concentration initially appears when GFR decreases to less than 20% to 25% of normal.3, 20, 21, 22 At this level of GFR, it is likely that approximately 80% of patients will manifest some degree of hypobicarbonatemia.7, 8, 22 The metabolic acidosis and accompanying acidemia generally are mild to moderate in degree, with plasma bicarbonate concentrations ranging

Clinical characteristics of acid-base parameters in dialysis patients

This topic recently was reviewed by us and others.15, 45 As noted, after patients develop end-stage renal failure, the majority will have metabolic acidosis.7 Theoretically, after maintenance hemodialysis therapy has been established and bicarbonate stores have been repleted, delivery of base during the usual thrice-weekly dialysis procedure would be anticipated to return predialysis plasma bicarbonate concentrations to normal values of 24 to 25 mEq/L (mmol/L). However, with a dialysate

Clinical effects of metabolic acidosis in patients with CKD

Experimental studies in animals and clinical studies of humans have shown that chronic metabolic acidosis can have diverse deleterious effects on organ function (Table 2).

Some experimental studies examining the impact of metabolic acidosis on organ function were performed in individuals with completely normal renal function,54, 55, 56 and these findings have been inferred to also apply to patients with CKD because this disorder is the most common cause of metabolic acidosis lasting for more

Treatment of metabolic acidosis in patients with CKD

Because metabolic acidosis in patients with CKD appears to be associated with significant clinical abnormalities, several investigators examined the impact of treating the metabolic acidosis. Studies were performed in patients with CKD before and after the initiation of long-term maintenance dialysis therapy. Metabolic acidosis was corrected by the administration of base, alteration in dialysate base concentration, or both. In some studies, metabolic acidosis was completely normalized, whereas

References (133)

  • R.C. Morris et al.

    Renal acidosis

    Kidney Int

    (1972)
  • J. Uribarri et al.

    A re-evaluation of the urinary parameters of acid production and excretion in patients with chronic renal acidosis

    Kidney Int

    (1995)
  • G.H. Kim et al.

    Evaluation of urine acidification by urine anion gap and urine osmolar gap in chronic metabolic acidosis

    Am J Kidney Dis

    (1996)
  • N. Lameire et al.

    Influence of progressive salt restriction on urinary bicarbonate wasting in uremic acidosis

    Am J Kidney Dis

    (1986)
  • R. Mehrotra et al.

    Metabolic acidosis in maintenance dialysis patientsClinical considerations

    Kidney Int Suppl

    (2003)
  • J. Uribarri et al.

    Association of acidosis and nutritional parameters in hemodialysis patients

    Am J Kidney Dis

    (1999)
  • B. Kirschbaum

    Spurious metabolic acidosis in hemodialysis patients

    Am J Kidney Dis

    (2000)
  • B. Kirschbaum

    Effect of high bicarbonate hemodialysis on ionized calcium and risk of metastatic calcification

    Clin Chim Acta

    (2004)
  • S. Mujais

    Acid-base profile in patients on PD

    Kidney Int Suppl

    (2003)
  • M. Brungger et al.

    Effect of chronic metabolic acidosis on the growth hormone IGF-1 endocrine axisNew cause of growth hormone insensitivity in humans

    Kidney Int

    (1997)
  • R.G. Roberts et al.

    The correction of acidosis does not increase dietary protein intake in chronic renal failure patients

    Am J Kidney Dis

    (1996)
  • A. Lefebvre et al.

    Optimal correction of acidosis changes progression of dialysis osteodystrophy

    Kidney Int

    (1989)
  • J.A. Kraut et al.

    The effects of metabolic acidosis on bone formation and bone resorption in the rat

    Kidney Int

    (1986)
  • S. Domrongkitchaiporn et al.

    Bone histology and bone mineral density after correction of acidosis in distal renal tubular acidosis

    Kidney Int

    (2002)
  • W.E. Mitch et al.

    Mechanisms activated by kidney disease and the loss of muscle mass

    Am J Kidney Dis

    (2001)
  • W.E. Mitch et al.

    Mechanisms activating proteolysis to cause muscle atrophy in catabolic conditions

    J Ren Nutr

    (2003)
  • W.E. Mitch

    Mechanisms causing loss of lean body mass in kidney disease

    Am J Clin Nutr

    (1998)
  • R.C. May et al.

    Glucocorticoids and acidosis stimulate protein and amino acid catabolism in vivo

    Kidney Int

    (1996)
  • N.J. Papadoyannakis et al.

    The effect of the correction of metabolic acidosis on nitrogen and protein balance of patients with chronic renal failure

    Am J Clin Nutr

    (1984)
  • W.P. Pickering et al.

    Nutrition in CAPDSerum bicarbonate and the ubiquitin-proteasome system in muscle

    Kidney Int

    (2002)
  • C. Verove et al.

    Effect of the correction of metabolic acidosis on nutritional status in elderly patients with chronic renal failure

    J Ren Nutr

    (2002)
  • J.P. Brady et al.

    Correction of metabolic acidosis and its effect on albumin in chronic hemodialysis patients

    Am J Kidney Dis

    (1998)
  • B. Moller

    The hydrogen ion concentration in arterial blood

    Acta Med Scand

    (1959)
  • J.R. Elkington

    Hydrogen ion turnover in renal health and disease

    Ann Intern Med

    (1962)
  • W.B. Schwartz et al.

    On the mechanism of acidosis in chronic renal disease

    J Clin Invest

    (1959)
  • I. Kurtz et al.

    The importance of renal ammonia metabolism to whole-body acid-base-balance—A reanalysis of the pathophysiology of renal tubular-acidosis

    Miner Electrolyte Metab

    (1990)
  • A.S. Relman

    Renal acidosis and renal excretion of acid in health and disease

    Adv Intern Med

    (1964)
  • C.M. Clase et al.

    Prevalence of low glomerular filtration rate in nondiabetic AmericansThird National Health and Nutrition Examination Survey (NHANES III)

    J Am Soc Nephrol

    (2002)
  • L. Frassetto et al.

    Age and systemic acid-base equilibriumAnalysis of published data

    J Gerontol

    (1996)
  • R.C. May et al.

    Mechanisms for defects in muscle protein metabolism in rats with chronic uremiaThe influence of metabolic acidosis

    J Clin Invest

    (1987)
  • M.S. Oh et al.

    What unique acid-base considerations exist in dialysis patients?

    Semin Dial

    (2004)
  • C.Y. Hsu et al.

    Elevations of serum phosphorus and potassium in mild to moderate chronic renal insufficiency

    Nephrol Dial Transplant

    (2002)
  • L.A. Frassetto et al.

    Effect of age on blood acid-base composition in adult humans. Role of age-related renal functional decline

    Am J Physiol

    (1996)
  • B. Widmer et al.

    Serum electrolytes and acid base compositionThe influence of graded degrees of chronic renal failure

    Arch Intern Med

    (1979)
  • D.P. Simpson

    Control of hydrogen ion homeostasis and renal acidosis

    Medicine

    (1971)
  • N.G. De Santo et al.

    Effect of an acute oral protein load on renal acidification in healthy humans and in patients with chronic renal failure

    J Am Soc Nephrol

    (1997)
  • S. Ray et al.

    Acid excretion and serum electrolyte patterns in patients with advanced chronic renal failure

    Miner Electrolyte Metab

    (1990)
  • A. Ong et al.

    Loss of glomerular function and tubulointerstitial fibrosisCause or effect?

    Kidney Int

    (1992)
  • A.D. Goodman et al.

    Production, excretion, and net balance of fixed acid in patients with renal acidosis

    J Clin Invest

    (1965)
  • P.D. Dass et al.

    Renal ammonia and bicarbonate production in chronic renal failure

    Miner Electrolyte Metab

    (1990)
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    Supported in part by the Veterans Administration (J.A.K.); Max Factor Family Foundation; the Richard and Hinda Rosenthal Foundation, and the Fredericka Taublitz Fund (I.K.).

    Originally published online as doi:10.1053/j.ajkd.2005.03.003 on April 29, 2005.

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