Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Podcasts
    • Subject Collections
    • Archives
    • ASN Meeting Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
    • Reprint Information
  • Trainees
    • Peer Review Program
    • Prize Competition
  • About CJASN
    • About CJASN
    • Editorial Team
    • CJASN Impact
    • CJASN Recognitions
  • More
    • Alerts
    • Advertising
    • Reprint Information
    • Subscriptions
    • Feedback
  • ASN Kidney News
  • Other
    • JASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • JASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Podcasts
    • Subject Collections
    • Archives
    • ASN Meeting Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
    • Reprint Information
  • Trainees
    • Peer Review Program
    • Prize Competition
  • About CJASN
    • About CJASN
    • Editorial Team
    • CJASN Impact
    • CJASN Recognitions
  • More
    • Alerts
    • Advertising
    • Reprint Information
    • Subscriptions
    • Feedback
  • ASN Kidney News
  • Visit ASN on Facebook
  • Follow CJASN on Twitter
  • CJASN RSS
  • Community Forum
Kidney Case Conference: Nephrology Quiz and Questionnaire
You have accessRestricted Access

Metabolic Acidosis in a Patient with CKD

Qi Qian
CJASN August 2019, 14 (8) 1245-1247; DOI: https://doi.org/10.2215/CJN.00600119
Qi Qian
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Qi Qian
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading
  • Metabolic acidosis
  • CKD progression
  • alkali therapy
  • fruits and vegetables
  • dietary salt
  • guanolyn peptides
  • electrolytes
  • Diagnostic Tests, Routine
  • Acid-Base Imbalance

Introduction

A 62-year-old woman with hypertension, hyperlipidemia, and CKD stage 3b presented for a routine evaluation. Her medications included lisinopril 10 mg daily, hydrochlorothiazide 12.5 mg daily, metoprolol succinate 50 mg daily, rosuvastatin 10 mg daily, and baby aspirin. She is a nonsmoker and had been on a regular diet.

Physical examination showed a well-developed female with body mass index of 28.0 kg/m2, BP of 136/62 mm Hg, and heart rate of 65/min. The rest of the examination was unremarkable.

Laboratory studies revealed serum sodium (Na+) of 136 mEq/L, potassium (K+) of 4.1 mEq/L, bicarbonate (HCO3−) of 22 mEq/L, and creatinine of 1.7 mg/dl (eGFR=32 ml/min per 1.73 m2). Urine protein-to-creatinine ratio was 0.3, and microscopy was normal.

Question 1

Which of the following regarding acid-base regulation in CKD is correct?

  • A. Net endogenous acid production (NEAP) is minimally modifiable by diet change.

  • B. Dietary salt can be a source of acid, contributing to acidosis.

  • C. Guanylin and uroguanylin (UGN), through pendrin, play a role in Cl− retention and acidosis.

  • D. Plant proteins and animal proteins show a similar degree of acidogenesis.

Discussion of Question 1

The correct answer is B.

Dietary intake of acid and base precursors, metabolized to nonvolatile acidic and alkali products, is the major determinant of NEAP (net sum of acids-alkali); NEAP can thus be modified by varying diet (1). A is incorrect. Western diet generates approximately 0.7–1.0 mEq/kg body wt per day of net noncarbonic (nonvolatile) acids (approximately 50–100 mEq of daily NEAP) that rely on kidneys to excrete, chiefly in the form of ammonium and phosphoric salts. Kidney dysfunction impairs acid excretion capacity; without modifying NEAP, H+ surplus will predictably emerge and herald metabolic acidosis, which progressively worsens with CKD progression. Dietary modifications (i.e., adding base-generating fruits/vegetables and avoiding overconsumption of acidogenic meats and processed grains) can reduce NEAP, thereby minimizing H+ buildup.

The Western diet contains high levels of salt (sodium chloride), mostly 10 to >12 g/d. Given the equimolar Na+ and Cl− in salt and approximately 140:100 Na+/Cl− ratio in plasma, salt ingestion adds disproportionately more Cl− into the body, and if unadjusted, it can cause hyperchloremia. The Cl− increase leads to a reduction in OH− (body fluid electroneutrality); the OH− reduction obligates H+ elevation (ionic product constant of water: Kw = [H+] × [OH−]). Sodium chloride addition also dilutes serum HCO3−. The composite outcome of these equilibrium shifts is acidosis, analogous to the much simpler low pH (5.4) for 0.9% saline (2).

Despite dietary salt loading, however, only minute (subclinical) acid-base deviations are observed in healthy adults (3). Such apparent tolerance is due to the presence of efficient homeostatic regulatory machinery, residing primarily in the gut and kidney (Figure 1). In the gut, guanolyn peptides (guanylin/UGN [4,5]) deter Na+ and Cl− absorption by blocking Na+/H+ exchanger and stimulating cystic fibrosis transmembrane conductance regulator. In the kidney proximal tubules, through suppressing Na+/H+ exchanger and modulating membrane potential, UGN reduces net absorption of Na+, Cl−, and K+. In the distal tubules, in addition to blunting Na+ and K+ absorption, UGN inhibits the expression of pendrin (a Cl−/HCO3− exchanger) in the (non-α) intercalated cells, preventing Cl− absorption in exchange for HCO3−. Lower tubular fluid HCO3− also blunts HCO3−-stimulated epithelial Na+ channel activity, further tempering Na+ absorption. C is incorrect. In patients with CKD, loss of functional kidney mass diminishes such a tight regulation, contributing to Na+ and Cl− retention, volume expansion, and acidosis.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Salt absorption is regulated by guanolyn peptides in the gut and kidney. Intake of salt (sodium chloride [NaCl])-containing meals is associated with the genesis and secretion of guanolyn peptides (guanolyn [GN] and uroguanolyn [UGN]) in the gut. The guanylate cyclase-C (GC-C) receptors, when activated by GN/UGN, increase intracellular cyclic guanosine monophosphate (cGMP), which in turn, activates protein kinases (protein kinase G [PKG] and protein kinase A [PKA; via phosphodiesterase inhibition]) and ion channels, including cystic fibrosis transmembrane conductance regulator (CFTR), stimulating secretion of NaCl-containing fluids. In the kidney, UGN activates G protein–coupled receptor (GPCR), modulates membrane potential in the proximal tubular cells, and inhibits renal outer medullary potassium channel (ROMK) in the distal tubular cells (mainly the principle cells). Through a yet to be identified mechanism, UGN inhibits pendrin expression in the non–α-intercalated cells. Note that the figure is an abbreviated illustration of GN/UGN regulations related to NaCl. ENaC, epithelial sodium channel; GTP, guanosine triphosphate; NHE, Na+/H+ exchanger; PDE, phosphodiesterase.

Dietary proteins are metabolized to amino acids, which can be further broken down to yield acidic and alkaline products. Metabolizing animal proteins generates net acidic products (hydrogen chloride, sulfuric acid, and phosphoric acid). Vegetable proteins, especially soy protein, contain less acid-producing methionine, cysteine, lysine, and phosphorous and elicit minimal adaptive glomerular hyperfiltration as do animal proteins (6). Diets richer in plant foods are, in general, less acidogenic, and they are associated with better kidney function (7), whereas diets heavy in animal foods can be deleterious (8). D is incorrect.

Question 2

What should be the next step in the management of this patient?

  • A. No change in the current management

  • B. Dietary consultation to increase intake of fruits and vegetables

  • C. Add sodium bicarbonate (NaHCO3)

  • D. Add NaHCO3 and avoid fruits and vegetables to prevent hyperkalemia

Discussion of Question 2

The correct answer is B.

Despite frequent occurrence of acid surplus in patients with CKD on an acidogenic diet, large drops in serum HCO3− (or total CO2) are minimized by augmenting multiple intrarenal and systemic compensatory mechanisms. These mechanisms include (1) enhanced kidney acid excretion in the form of NH3/NH4+ (high capacity) and titratable acids (low capacity) and (2) titration of excess acids by non-HCO3− buffers, including intra- and extracellular proteins and skeletal sources of bases (calcium carbonate and dibasic phosphate). The parallel release of calcium from bones can cause vascular and soft tissue calcification accompanied by bone demineralization. Acidosis has also been shown to elevate plasma fibroblast growth factor 23, a phosphatonin that, when elevated, is associated with an increased risk of cardiovascular disease. Collectively, sustained acid surplus and its induced compensatory reactions are proportionally associated with intrarenal accumulation of inflammatory and fibrogenic mediators (endothelin-1, angiotensin II, and aldosterone), systemic inflammation, muscle catabolism/wasting, osteodystrophy, CKD progression, cardiovascular complications, and all-cause mortality.

The importance of acid surplus in these deleterious outcomes is substantiated by consistent observations that, after eliminating or reducing acidic intakes in CKD animal models and patients with CKD, the deleterious sequelae can be dramatically curtailed. More relevant to our patient, Goraya et al. (9) showed that, in nondiabetic patients with CKD stage 3 (n=108) without overt acidosis (serum HCO3−≥22 mEq/L), reducing NEAP by supplanting alkali (NaHCO3) or fruits and vegetables reduces urine angiotensinogen and slows CKD progression. Additionally, compared with NaHCO3, supplementing fruits/vegetables resulted in a small but significant reduction in body weight and BP. Plant foods also contain less bioavailable phosphorous. In a crossover study of nine patients with a mean eGFR of 32 ml/min, a 1-week vegetarian diet lowered serum phosphorus and fibroblast growth factor 23 compared with a meat-containing diet with equivalent amounts of phosphorous (10). Dietary modification, therefore, should be an integral part of CKD care. A is incorrect. Dietary information from the National Kidney Foundation can be obtained at https://www.kidney.org/nutrition/Kidney-Disease-Stages-1-4.

Although NaHCO3 administration could be beneficial for patients with subclinical acidosis (plasma total CO2 of 22–24 mmol/L), the current recommendation is to initiate alkaline therapy when serum HCO3− falls below 22 mEq/L. C is incorrect. Fruit/vegetable supplementation (equivalent to 50% of dietary acid load) for nondiabetic patients with moderate CKD seems well tolerated and does not have added risk of hyperkalemia. D is incorrect. In practice, however, it would be prudent to monitor serum K+ after modifying diet and take into account other confounding intakes, such as K+-sparing diuretics and salt substitutes. In circumstances of fruit/vegetable intolerance, oral alkali may be considered. Conversely, hypokalemia (K+<4 mEq/L), common (approximately 25%–50%) in CKD, is also detrimental. It stimulates kidney ammonia genesis and is linked to systemic inflammation, oxidative stress, hypertension, CKD progression, and cardiovascular mortality. NaHCO3 notably augments urinary K+ loss, whereas dietary enrichment of fruits and vegetables can prevent K+ deficit; it has the added benefits of a rich fiber supply, fostering healthier bowel microbiota, intestinal mucosa, and gut transit, thereby limiting uremic toxin generation. Thus, fruits and vegetables, when tolerated, are comparatively more advantageous than NaHCO3.

Disclosures

Dr. Qian has nothing to disclose.

Acknowledgments

For most American Society of Nephrology (ASN) Kidney Week attendees, case-based clinical nephrology talks are one of the most exciting venues. The Nephrology Quiz and Questionnaire (NQ&Q) is the essence of clinical nephrology and represents what drew all of us into the field of nephrology. The expert discussants prepared vignettes of puzzling cases, which illustrated some topical, chal-lenging, or controversial aspect of the diagnosis or management of key clinical areas of nephrology. These cases were presented and eloquently discussed by our four expert ASN faculty. Subsequently, each discussant prepared a manuscript summarizing his or her case discussions, which serves as the main text of this article (Mark A. Perazella and Michael Choi, Comoderators).

Footnotes

  • Published online ahead of print. Publication date available at www.cjasn.org.

  • Copyright © 2019 by the American Society of Nephrology

References

  1. ↵
    1. Kurtz I,
    2. Maher T,
    3. Hulter HN,
    4. Schambelan M,
    5. Sebastian A
    : Effect of diet on plasma acid-base composition in normal humans. Kidney Int 24: 670–680, 1983
    OpenUrlCrossRefPubMed
  2. ↵
    1. Li H,
    2. Sun SR,
    3. Yap JQ,
    4. Chen JH,
    5. Qian Q
    : 0.9% saline is neither normal nor physiological. J Zhejiang Univ Sci B 17: 181–187, 2016
    OpenUrl
  3. ↵
    1. Frassetto LA,
    2. Morris RC Jr.,
    3. Sebastian A
    : Dietary sodium chloride intake independently predicts the degree of hyperchloremic metabolic acidosis in healthy humans consuming a net acid-producing diet. Am J Physiol Renal Physiol 293: F521–F525, 2007
    OpenUrlCrossRefPubMed
  4. ↵
    1. Wiegand RC,
    2. Kato J,
    3. Huang MD,
    4. Fok KF,
    5. Kachur JF,
    6. Currie MG
    : Human guanylin: cDNA isolation, structure, and activity. FEBS Lett 311: 150–154, 1992
    OpenUrlCrossRefPubMed
  5. ↵
    1. Kita T,
    2. Smith CE,
    3. Fok KF,
    4. Duffin KL,
    5. Moore WM,
    6. Karabatsos PJ,
    7. Kachur JF,
    8. Hamra FK,
    9. Pidhorodeckyj NV,
    10. Forte LR,
    11. Currie MG
    : Characterization of human uroguanylin: A member of the guanylin peptide family. Am J Physiol 266: F342–F348, 1994
    OpenUrl
  6. ↵
    1. Kontessis P,
    2. Jones S,
    3. Dodds R,
    4. Trevisan R,
    5. Nosadini R,
    6. Fioretto P,
    7. Borsato M,
    8. Sacerdoti D,
    9. Viberti G
    : Renal, metabolic and hormonal responses to ingestion of animal and vegetable proteins. Kidney Int 38: 136–144, 1990
    OpenUrlCrossRefPubMed
  7. ↵
    1. Chrysohoou C,
    2. Panagiotakos DB,
    3. Pitsavos C,
    4. Skoumas J,
    5. Zeimbekis A,
    6. Kastorini CM,
    7. Stefanadis C
    : Adherence to the Mediterranean diet is associated with renal function among healthy adults: The ATTICA study. J Ren Nutr 20: 176–184, 2010
    OpenUrlCrossRefPubMed
  8. ↵
    1. Ma J,
    2. Jacques PF,
    3. Hwang SJ,
    4. Troy LM,
    5. McKeown NM,
    6. Chu AY,
    7. Fox CS
    : Dietary guideline adherence index and kidney Measures in the Framingham heart study. Am J Kidney Dis 68: 703–715, 2016
    OpenUrlPubMed
  9. ↵
    1. Goraya N,
    2. Simoni J,
    3. Jo CH,
    4. Wesson DE
    : 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. Kidney Int 86: 1031–1038, 2014
    OpenUrlCrossRefPubMed
  10. ↵
    1. Moe SM,
    2. Zidehsarai MP,
    3. Chambers MA,
    4. Jackman LA,
    5. Radcliffe JS,
    6. Trevino LL,
    7. Donahue SE,
    8. Asplin JR
    : Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. Clin J Am Soc Nephrol 6: 257–264, 2011
    OpenUrlAbstract/FREE Full Text
PreviousNext
Back to top

In this issue

Clinical Journal of the American Society of Nephrology: 14 (8)
Clinical Journal of the American Society of Nephrology
Vol. 14, Issue 8
August 07, 2019
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in CJASN.
Enter multiple addresses on separate lines or separate them with commas.
Metabolic Acidosis in a Patient with CKD
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Metabolic Acidosis in a Patient with CKD
Qi Qian
CJASN Aug 2019, 14 (8) 1245-1247; DOI: 10.2215/CJN.00600119

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Metabolic Acidosis in a Patient with CKD
Qi Qian
CJASN Aug 2019, 14 (8) 1245-1247; DOI: 10.2215/CJN.00600119
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Introduction
    • Question 1
    • Discussion of Question 1
    • Question 2
    • Discussion of Question 2
    • Disclosures
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

  • Use of Checkpoint Inhibitors in a Kidney Transplant Recipient with Metastatic Cancer
  • A Case of Nephrotic Syndrome after Allogeneic Stem Cell Transplantation
Show more Kidney Case Conference: Nephrology Quiz and Questionnaire

Cited By...

  • No citing articles found.
  • Google Scholar

Similar Articles

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Keywords

  • metabolic acidosis
  • CKD progression
  • alkali therapy
  • fruits and vegetables
  • dietary salt
  • guanolyn peptides
  • electrolytes
  • Diagnostic Tests, Routine
  • Acid-Base Imbalance

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Trainee of the Year
  • Author Resources
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • CJASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About CJASN
  • CJASN Email Alerts
  • CJASN Key Impact Information
  • CJASN Podcasts
  • CJASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe

© 2021 American Society of Nephrology

Print ISSN - 1555-9041 Online ISSN - 1555-905X

Powered by HighWire