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
Editorials
You have accessRestricted Access

Staying on Target with Continuous Dialysis

Sevag Demirjian and William H. Fissell
CJASN January 2015, 10 (1) 7-8; DOI: https://doi.org/10.2215/CJN.11251114
Sevag Demirjian
*Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William H. Fissell
†Department of Nephrology and Hypertension, Vanderbilt University, Nashville, Tennessee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • View PDF
Loading
  • acute renal failure
  • dialysis
  • pharmacokinetics
  • phosphate uptake

“It was through the evolution of this filtration-reabsorption system that the kidney came to be almost entirely responsible for the composition of the internal environment of the body, manufacturing it, as we have said, in reverse, by saving some things from the glomerular filtrate and rejecting others. Among the substances known to be reabsorbed by the tubules in man, for example, are water, sodium, potassium, calcium, chloride, bicarbonate, phosphate, sulfate, glucose, fructose, a large variety of amino acids, and several vitamins and hormones. There are certainly many others on which no quantitative observations are available.” (1)

As the proverbial primitive man and woman ventured on to dry land, their kidneys continued to excrete wastes, but now with extreme frugality of water and salt. Kidneys had to accomplish high-volume filtration, as in their previous marine habitat, so they could excrete novel toxins and filter and secrete metabolic wastes, but now they had to also perpetually reabsorb salt and water in the tubule. Some additional solutes are reabsorbed so completely that their clearance approaches zero, whereas others are actively secreted so that their clearance approaches renal plasma flow. Inasmuch as filtration has become synonymous with renal function in the context of RRT, it is easy to overlook the robust and dynamic contribution of the renal tubule to homeostasis.

Almost four decades have passed since Kramer et al. (2) and Paganini et al. (3) introduced and popularized an ingeniously simple modality of dialysis. Continuous dialysis capitalized on advances of membrane technology and promised more physiologic and continuous renal support in the bed-bound critically ill patient. The opportunity to provide continuous small solute clearance raised the question of dose targeting: when compared with a healthy glomerular filtration rate of 120–140 ml/min, what is the best dose of continuous renal replacement to prescribe? Two large well-conducted studies failed to demonstrate improved survival with increased dialysis dose in the critically ill patient (4,5). We have conclusively exhausted that line of inquiry. As we increased dialysis duration in pursuit of the very high standard set by glomerular filtration, we perhaps once more underestimated the contribution of the renal tubule to homeostasis. Our bedside gadgets are incomplete mimics of the organs refined by millions of years of ceaseless tinkering by Mother Nature, and continuous RRT (CRRT) removes small solutes, including amino acids, vitamins, trace elements, hormones, minerals, antibiotics and vasopressors, and wastes and water. As the CRRT dose increases, so do the off-target effects of therapy (6–9).

It is established that phosphate removal during intermittent dialysis does not follow the same linear two-compartment kinetics of urea (10,11). Phosphate is effectively removed with increased frequency or duration of dialysis treatments (12). In this issue of the journal, Sharma et al. report measureable reductions in red blood cell concentration of 2,3 diphosphoglycerate contemporaneous with CRRT-induced phosphate depletion (13). Although the study based its conclusions on a relatively small sample size, it highlights the significant cumulative phosphate drain with time and its putative downstream mediator effect on tissue oxygen delivery in the critically ill patient (14). Moreover, CRRT-induced alkalemia, another dose-dependent side effect that follows a similar temporal pattern, will also shift the oxygen-hemoglobin curve further to the left because of the Bohr effect (reduces oxygen release in peripheral tissues) (15). This is especially disconcerting in this patient population where compromised oxygenation in the setting of renal failure, further compounded by volume burden, is the main determinant of mortality (16).

Continuous renal support saves lives by correcting electrolyte and acid-base derangements and controlling extracellular fluid volume in the critically ill. Nephrologists aspire to improve the disappointing survival rates in severe AKI, and the results of the VA/NIH Acute Renal Failure Trial Network Study and the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy Study trials have redirected us from a focus on urea clearance to considering middle molecules and protein-bound solutes. Clearance of middle molecules and protein-bound uremic solutes will require increases in blood and dialysate flow rates (17–22). In an ideal scenario, we would know the identities of the molecular mediators of uremia and adjust dialysis settings to optimize their clearance. It is becoming more apparent that the off-target effects of CRRT, particularly depletion of needed metabolites and removal of essential drugs, are an underexplored opportunity to improve outcomes in severe AKI. Sharma and colleagues have added an important and novel mechanism by which unanticipated off-target effects of CRRT could undermine our efforts to support the critically ill patient.

Disclosures

None.

Footnotes

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

  • See related article, “Reductions in Red Blood Cell 2,3-Diphosphoglycerate Concentration during Continuous Renal Replacment Therapy,” on pages 74–79.

  • Copyright © 2015 by the American Society of Nephrology

References

  1. 1.↵
    1. Smith HJ
    From Fish to Philosopher: The Story of Our Internal Environment, Boston, Little Brown & Co., 1959
  2. 2.↵
    1. Kramer P,
    2. Wigger W,
    3. Rieger J,
    4. Matthaei D,
    5. Scheler F
    : [Arteriovenous haemofiltration: a new and simple method for treatment of over-hydrated patients resistant to diuretics]. Klin Wochenschr 55: 1121–1122, 1977
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Paganini EP,
    2. Nakamoto S
    : Continuous slow ultrafiltration in oliguric acute renal failure. Trans Am Soc Artif Intern Organs 26: 201–204, 1980
    OpenUrlPubMed
  4. 4.↵
    1. Bellomo R,
    2. McGrath B,
    3. Boyce N
    : Effect of continuous venovenous hemofiltration with dialysis on hormone and catecholamine clearance in critically ill patients with acute renal failure. Crit Care Med 22: 833–837, 1994
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Palevsky PM,
    2. Zhang JH,
    3. O'Connor TZ
    : Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 359: 7–20, 2008
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Connor MJ Jr.,
    2. Salem C,
    3. Bauer SR,
    4. Hofmann CL,
    5. Groszek J,
    6. Butler R,
    7. Rehm SJ,
    8. Fissell WH
    : Therapeutic drug monitoring of piperacillin-tazobactam using spent dialysate effluent in patients receiving continuous venovenous hemodialysis. Antimicrob Agents Chemother 55: 557–560, 2011
    OpenUrlAbstract/FREE Full Text
  7. 7.
    1. Bauer SR,
    2. Salem C,
    3. Connor MJ Jr.,
    4. Groszek J,
    5. Taylor ME,
    6. Wei P,
    7. Tolwani AJ,
    8. Fissell WH
    : Pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in 42 patients treated with concomitant CRRT. Clin J Am Soc Nephrol 7: 452–457, 2012
    OpenUrlAbstract/FREE Full Text
  8. 8.
    1. Afshartous D,
    2. Bauer SR,
    3. Connor MJ,
    4. Aduroja OA,
    5. Amde M,
    6. Salem C,
    7. Groszek JJ,
    8. Fissell WH
    : Pharmacokinetics and pharmacodynamics of imipenem and meropenem in critically ill patients treated with continuous venovenous hemodialysis. Am J Kidney Dis 63: 170–171, 2014
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Nolin TD,
    2. Aronoff GR,
    3. Fissell WH,
    4. Jain L,
    5. Madabushi R,
    6. Reynolds K,
    7. Zhang L,
    8. Huang SM,
    9. Mehrotra R,
    10. Flessner MF,
    11. Leypoldt JK,
    12. Witcher JW,
    13. Zineh I,
    14. Archdeacon P,
    15. Roy-Chaudhury P,
    16. Goldstein SL
    : Pharmacokinetic assessment in patients receiving continuous RRT: Perspectives from the Kidney Health Initiative [published online ahead of print September 4, 2014]. Clin J Am Soc Nephrol
  10. 10.↵
    1. Haas T,
    2. Hillion D,
    3. Dongradi G
    : Phosphate kinetics in dialysis patients. Nephrol Dial Transplant 6[Suppl 2]: 108–113, 1991
    OpenUrlPubMed
  11. 11.↵
    1. Spalding EM,
    2. Chamney PW,
    3. Farrington K
    : Phosphate kinetics during hemodialysis: Evidence for biphasic regulation. Kidney Int 61: 655–667, 2002
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Mucsi I,
    2. Hercz G,
    3. Uldall R,
    4. Ouwendyk M,
    5. Francoeur R,
    6. Pierratos A
    : Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis. Kidney Int 53: 1399–1404, 1998
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Sharma S,
    2. Brugnara C,
    3. Betensky RA,
    4. Waikar SS
    : Reductions in red blood cell 2,3 diphosphoglycerate concentration during continuous renal replacement therapy. Clin J Am Soc Nephrol 10: 74–79, 2015
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Demirjian S,
    2. Teo BW,
    3. Guzman JA,
    4. Heyka RJ,
    5. Paganini EP,
    6. Fissell WH,
    7. Schold JD,
    8. Schreiber MJ
    : Hypophosphatemia during continuous hemodialysis is associated with prolonged respiratory failure in patients with acute kidney injury. Nephrol Dial Transplant 26: 3508–3514, 2011
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Demirjian S,
    2. Teo BW,
    3. Paganini EP
    : Alkalemia during continuous renal replacement therapy and mortality in critically ill patients. Crit Care Med 36: 1513–1517, 2008
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Demirjian S,
    2. Chertow GM,
    3. Zhang JH,
    4. O’Connor TZ,
    5. Vitale J,
    6. Paganini EP,
    7. Palevsky PM
    ; VA/NIH Acute Renal Failure Trial Network: Model to predict mortality in critically ill adults with acute kidney injury. Clin J Am Soc Nephrol 6: 2114–2120, 2011
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    1. Scribner BH,
    2. Babb AL
    : Evidence for toxins of “middle” molecular weight. Kidney Int Suppl (3): 349–351, 1975
  18. 18.
    1. Vanholder RC,
    2. De Smet RV,
    3. Ringoir SM
    : Assessment of urea and other uremic markers for quantification of dialysis efficacy. Clin Chem 38: 1429–1436, 1992
    OpenUrlAbstract/FREE Full Text
  19. 19.
    1. Lesaffer G,
    2. De Smet R,
    3. Lameire N,
    4. Dhondt A,
    5. Duym P,
    6. Vanholder R
    : Intradialytic removal of protein-bound uraemic toxins: role of solute characteristics and of dialyser membrane. Nephrol Dial Transplant 15: 50–57, 2000
    OpenUrlCrossRefPubMed
  20. 20.
    1. Meyer TW,
    2. Walther JL,
    3. Pagtalunan ME,
    4. Martinez AW,
    5. Torkamani A,
    6. Fong PD,
    7. Recht NS,
    8. Robertson CR,
    9. Hostetter TH
    : The clearance of protein-bound solutes by hemofiltration and hemodiafiltration. Kidney Int 68: 867–877, 2005
    OpenUrlCrossRefPubMed
  21. 21.
    1. Jourde-Chiche N,
    2. Dou L,
    3. Cerini C,
    4. Dignat-George F,
    5. Vanholder R,
    6. Brunet P
    : Protein-bound toxins—update 2009. Semin Dial 22: 334–339, 2009
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Hofmann CL,
    2. Fissell WH
    : Middle-molecule clearance at 20 and 35 ml/kg/h in continuous venovenous hemodiafiltration. Blood Purif 29: 259–263, 2010
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

Clinical Journal of the American Society of Nephrology: 10 (1)
Clinical Journal of the American Society of Nephrology
Vol. 10, Issue 1
January 07, 2015
  • Table of Contents
  • Table of Contents (PDF)
  • 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.
Staying on Target with Continuous Dialysis
(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
Staying on Target with Continuous Dialysis
Sevag Demirjian, William H. Fissell
CJASN Jan 2015, 10 (1) 7-8; DOI: 10.2215/CJN.11251114

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Staying on Target with Continuous Dialysis
Sevag Demirjian, William H. Fissell
CJASN Jan 2015, 10 (1) 7-8; DOI: 10.2215/CJN.11251114
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
    • Disclosures
    • Footnotes
    • References
  • Info & Metrics
  • View PDF

More in this TOC Section

  • Opportunities for Improvement in Quality of Care of PD-Related Peritonitis in Children
  • Assessing Genetic Risk for IgA Nephropathy
  • Optimizing Utilization of Kidneys from Hepatitis C–Positive Kidney Donors
Show more Editorials

Cited By...

  • No citing articles found.
  • Google Scholar

Similar Articles

Related Articles

  • Reductions in Red Blood Cell 2,3-Diphosphoglycerate Concentration during Continuous Renal Replacment Therapy
  • PubMed
  • Google Scholar

Keywords

  • acute renal failure
  • dialysis
  • pharmacokinetics
  • phosphate uptake

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