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

Papadoyannakis, N.; Stefanidis, Constantinos; McGeown, Mary G.

doi:10.1093/ajcn/40.3.623

Cited by 199 publications

(81 citation statements)

References 18 publications

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“…It is important to emphasize that the spontaneous acidosis ofCRF, resulting from dietary protein, impairs both conservation ofbody nitrogen and muscle protein metabolism. The clinical importance of these findings is suggested by the report that NaHCO3 can improve the nitrogen balance of patients with CRF (33). Correction of acidosis either by alkali supplementation or by restricting dietary protein should be a goal of therapy.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms for defects in muscle protein metabolism in rats with chronic uremia. Influence of metabolic acidosis.

May¹,

Kelly²,

Mitch³

1987

J. Clin. Invest.

313

193

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Chronic renal failure (CRF) is associated with metabolic acidosis and abnormal muscle protein metabolism. As we have shown that acidosis by itself stimulates muscle protein degradation by a glucocorticoid-dependent mechanism, we assessed the contribution of acidosis to changes in muscle protein turnover in CRF. A stable model of uremia was achieved in partially nephrectomized rats (plasma urea nitrogen, 100-120 mg/dl, blood bicarbonate < 21 meq/liter). CRF rats excreted 22% more nitrogen than pair-fed controls (P < 0.005), so muscle protein synthesis and degradation were measured in perfused hindquarters. CRF rats had a 90% increase in net protein degradation (P < 0.001); this was corrected by dietary bicarbonate. Correction of acidosis did not reduce the elevated corticosterone excretion rate of CRF rats, nor did it improve a second defect in muscle protein turnover, a 34% lower rate of insulin-stimulated protein synthesis. Thus, abnormal nitrogen production in CRF is due to accelerated muscle proteolysis caused by acidosis and an acidosis-independent inhibition of insulin-stimulated muscle protein synthesis.

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Section: Discussionmentioning

confidence: 99%

Mechanisms for defects in muscle protein metabolism in rats with chronic uremia. Influence of metabolic acidosis.

May¹,

Kelly²,

Mitch³

1987

J. Clin. Invest.

313

193

View full text Add to dashboard Cite

show abstract

“…The fragment was subcloned into pGEM3zf (Promega Corp., Madison, WI) and the 513-base cRNA probe was synthesized in the presence of [a-32P]CTP (3,000 Ci/mmol) using T7 RNA polymerase. The RNA blot was prehybridized at 500C in 5 X Denhardt's solution, 1% SDS, 5 X 0.15 M NaCI, 0.01 M NaH2PO4, 1 M EDTA (SSPE), 50% deionized formamide, 10% polyethylene glycol containing 50 ,g/ml denatured herring testis DNA.…”

Section: Methodsmentioning

confidence: 99%

“…In normal adults, metabolic acidosis stimulates intracellular protein degradation and oxidation of branched-chain amino acids (2). Moreover, the nitrogen balance of patients with chronic renal failure improves when they are given sodium bicarbonate (3).…”

Section: Introductionmentioning

confidence: 99%

Metabolic acidosis stimulates muscle protein degradation by activating the adenosine triphosphate-dependent pathway involving ubiquitin and proteasomes.

Mitch¹,

Medina²,

Grieber³

et al. 1994

J. Clin. Invest.

362

182

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Metabolic acidosis often leads to loss of body protein due mainly to accelerated protein breakdown in muscle. To identify which proteolytic pathway is activated, we measured protein degradation in incubated epitrochlearis muscles from acidotic (NNH4CI-treated) and pair-fed rats under conditions that block different proteolytic systems. Inhibiting lysosomal and calcium-activated proteases did not reduce the acidosis-induced increase in muscle proteolysis. However, when ATP production was also blocked, proteolysis fell to the same low level in muscles of acidotic and control rats. Acidosis, therefore, stimulates selectively an ATP-dependent, nonlysosomal, proteolytic process.We also examined whether the activated pathway involves ubiquitin and proteasomes (multicatalytic proteinases). Acidosis was associated with a 2.5-to 4-fold increase in ubiquitin mRNA in muscle. There was no increase in muscle heat shock protein 70 mRNA or in kidney ubiquitin mRNA, suggesting specificity of the response. Ubiquitin mRNA in muscle returned to control levels within 24 h after cessation of acidosis. mRNA for subunits of the proteasome (C2 and C3) in muscle were also increased 4-fold and 2.5-fold, respectively, with acidosis; mRNA for cathepsin B did not change. These results are consistent with, but do not prove that acidosis stimulates muscle proteolysis by activating the ATP-ubiquitin-proteasomedependent, proteolytic pathway. (J. Clin. Invest. 1994. 93: 2127-2133

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“…Metabolic acidosis, in turn, may result in bone loss (2)(3)(4) and muscle wasting (5,6), prompting recommendations to maintain serum bicarbonate levels at 22 mEq/L or higher (7). Recently, lower serum bicarbonate has been shown to be a risk factor for CKD progression (8,9).…”

Section: Introductionmentioning

confidence: 99%

Estimated Net Endogenous Acid Production and Serum Bicarbonate in African Americans with Chronic Kidney Disease

Scialla

Appel

Astor

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Metabolic acidosis may contribute to morbidity and disease progression in patients with chronic kidney disease (CKD). The ratio of dietary protein, the major source of nonvolatile acid, to dietary potassium, which is naturally bound to alkali precursors, can be used to estimate net endogenous acid production (NEAP). We tested the association between estimated NEAP and serum bicarbonate in patients with CKD.Design, setting, participants, & measurements NEAP was estimated among 462 African American adults with hypertensive CKD using published equations:. Dietary protein and potassium intake were estimated from 24-hour urinary excretion of urea nitrogen and potassium, respectively. All of the eligible measurements during follow-up were modeled using generalized linear regression clustered by participant and adjusted for demographics, 24-hour urinary sodium, kidney function, and selected medications. ResultsHigher NEAP was associated with lower serum bicarbonate in a graded fashion (P trend Ͻ 0.001). Serum bicarbonate was 1.27 mEq/L lower among those in the highest compared with the lowest quartile of NEAP (P Ͻ 0.001). There was a greater difference in serum bicarbonate between the highest and lowest quartiles of NEAP among patients with stage 4/5 CKD (Ϫ2.43 mEq/L, P Ͻ 0.001) compared with those with stage 2/3 disease (Ϫ0.77 mEq/L, P ϭ 0.01; P-interaction ϭ 0.02). ConclusionsReducing NEAP, through reduction of dietary protein and increased intake of fruits and vegetables, may prevent metabolic acidosis in patients with CKD.

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

Cited by 199 publications

References 18 publications

Mechanisms for defects in muscle protein metabolism in rats with chronic uremia. Influence of metabolic acidosis.

Mechanisms for defects in muscle protein metabolism in rats with chronic uremia. Influence of metabolic acidosis.

Metabolic acidosis stimulates muscle protein degradation by activating the adenosine triphosphate-dependent pathway involving ubiquitin and proteasomes.

Estimated Net Endogenous Acid Production and Serum Bicarbonate in African Americans with Chronic Kidney Disease

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