JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Celik, I.
Right arrow Articles by Priebe, H.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Celik, I.
Right arrow Articles by Priebe, H.-J.

Anesth Analg 2004;99:309-310
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000127910.70670.87

LETTERS TO THE EDITOR

Renal Dysfunction After Hydroxyethyl Starch

Ilhan Celik, MD

Associate Professor, Institute of Theoretical Surgery, Philipps-University Marburg, Marburg, Germany

To the Editor:

On the basis of a literature review, Boldt and Priebe (1) advocate avoiding the use of the artificial colloid hydroxyethyl starch (HES) in patients with preexisting renal dysfunction. They acknowledge that most previous studies that failed to detect adverse renal effects of HES in low-risk patients used relatively insensitive markers such as urine output or circulating creatinine levels. In addition, they speculate that adverse renal effects might be avoided by use of HES with lower molecular weight (MW) and degree of substitution (DS), and they emphasize the importance of the HES C2/C6 ratio. However, current evidence indicates that adverse renal effects of HES are not dependent upon MW, DS, and C2/C6 ratio and that these effects are detectable both in low- and high-risk patients, as discussed below.

In a randomized trial of 60 major abdominal surgery patients (2), low molecular weight HES (MW, 70 kd; DS, 0.5; C2/C6, 4) impaired renal function, as evidenced by a 3.3-fold increase in {alpha}1-microglobulin in patients < 65 yr of age (P < 0.05) and a 2.0-fold increase among those > 65 yr (P < 0.05). A recent randomized trial by Boldt et al. (3) in 40 elderly cardiac surgery patients demonstrated renal impairment in recipients of HES (MW, 130 kd; DS, 0.4; C2/C6, 9), as judged by elevation of N-acetyl-ß-D-glucosamidase (P < 0.05), {alpha}1-microglobulin (P < 0.05), glutathione transferase-{alpha} (P < 0.05) and glutathione transferase-{pi} (P < 0.05) levels. The magnitude of the deleterious renal effects was similar to that of gelatin, an artificial colloid that has been shown to impair renal function compared with albumin in a randomized trial of 105 cardiac surgery patients (4).

Medium molecular weight HES (MW, 200 kd; DS, 0.5; C2/C6, 5) adversely affected renal function in a randomized trial of 25 hypovolemic surgical patients, as indicated by postoperative increases in N-acetyl-ß-D-glucosamidase (P < 0.05), {alpha}1-microglobulin (P < 0.05) and Tamm-Horsfall protein (P < 0.05) levels (5). Administration of HES (MW, 200 kd; DS, 0.62; C2/C6, 9) was an independent risk factor for acute renal failure in a multicenter randomized trial of 129 patients with severe sepsis or septic shock (6). In that trial the adjusted odds for acute renal failure were increased by 157% in HES recipients (odds ratio, 2.57; CI, 1.13–5.83).

Renal impairment is also seen with high molecular weight HES preparations used in the United States. In a retrospective study of 109 renal transplantation patients (7), postoperative serum creatinine was elevated (P < 0.05) in recipients of HES (MW, 450 kd; DS, 0.7; C2/C6, 4.6). In a retrospective study of 238 consecutive coronary artery bypass graft patients (8), use of HES (MW, 670 kd; DS, 0.75; C2/C6, unspecified) was independently associated with a reduction in glomerular filtration rate of 7.2 mL · min–1 · (1.73 m2)–1 per HES unit administered (CI, 1.7–12.7 mL · min–1 · (1.73 m2)–1; P = 0.012) on postoperative day 3 and 6.6 mL · min–1 · (1.73 m2)–1 (CI, 1.2–11.9 mL · min–1 · (1.73 m2)–1; P = 0.018) on day 5.

Thus, an adverse impact on renal function is apparent with HES molecular weights of 70, 130, 200, 450, and 670 kd, substitutions of 0.4, 0.5, 0.62, 0.7, and 0.75 and C2/C6 ratios of 4, 4.6, 5, and 9. This suggests that renal impairment is an inherent effect of HES. Furthermore, the effect was encountered in low-risk general surgery patients of NY Heart Association class I or II without preexisting renal or hepatic dysfunction (2) and intensive care unit patients without renal or circulatory dysfunction or sepsis (5), as well as higher risk patients undergoing renal transplantation (7) and cardiac surgery (3,8) or developing severe sepsis or septic shock (6). In a recently published prospective, randomized controlled clinical study in 21 male volunteers it was clearly demonstrated as expected that the application of polygeline and albumin during normovolemic hemodilution elicited both an early and a late histamine release (9). However, surprisingly medium molecular weight HES (MW, 200 kd; DS, 0.5; C2/C6, 5), which is regarded as a generally safe and effective plasma substitute, caused high incidences of early and late (67%) histamine release.

Unlike HES, the natural colloid albumin appears to exert a protective effect on the kidney. Albumin decreased the incidence of renal impairment from 33% to 10% (P = 0.002) and reduced hospital mortality from 29% to 10% (P = 0.01) in a randomized trial of 126 patients with spontaneous bacterial peritonitis (10). Albumin is also not associated with other complications of HES such as hemorrhage (11) and pruritus (12). Clearly, the contrasting safety profiles of HES and albumin need to be considered when making fluid management decisions.

References

  1. Boldt J, Priebe HJ. Intravascular volume replacement therapy with synthetic colloids: is there an influence on renal function? Anesth Analg 2003; 96: 376–82.[Abstract/Free Full Text]
  2. Kumle B, Boldt J, Piper S, et al. The influence of different intravascular volume replacement regimens on renal function in the elderly. Anesth Analg 1999; 89: 1124–30.[Abstract/Free Full Text]
  3. Boldt J, Brenner T, Lehmann A, et al. Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: comparison of a new starch preparation with gelatin. Intensive Care Med 2003; 29: 763–9.[Web of Science][Medline]
  4. Himpe D, van Cauwelaert P, Neels H, et al. Priming solutions for cardiopulmonary bypass: comparison of three colloids. J Cardiothorac Vasc Anesth 1991; 5: 457–66.[Medline]
  5. Dehne MG, Muhling J, Sablotzki A, et al. Effect of hydroxyethyl starch solution on kidney function in surgical intensive care patients. Anästhesiol Intensivmed Notfallmed Schmerzther 1997; 32: 348–54.[Web of Science][Medline]
  6. Schortgen F, Lacherade JC, Bruneel F, et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 2001; 357: 911–6.[Web of Science][Medline]
  7. Deman A, Peeters P, Sennesael J. Hydroxyethyl starch does not impair immediate renal function in kidney transplant recipients: a retrospective, multicentre analysis. Nephrol Dial Transplant 1999; 14: 1517–20.[Abstract/Free Full Text]
  8. Winkelmayer WC, Glynn RJ, Levin R, Avorn J. Hydroxyethyl starch and change in renal function in patients undergoing coronary artery bypass graft surgery. Kidney Int 2003; 64: 1046–9.[Web of Science][Medline]
  9. Celik I, Duda D, Stinner B, et al. Early and late histamine release induced by albumin, hetastarch and polygeline: some unexpected findings. Inflamm Res 2003; 52: 408–16.[Web of Science][Medline]
  10. Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999; 341: 403–9.[Abstract/Free Full Text]
  11. Wilkes MM, Navickis RJ, Sibbald WJ. Albumin versus hydroxyethyl starch in cardiopulmonary bypass surgery: a meta-analysis of postoperative bleeding. Ann Thorac Surg 2001; 72: 527–33.[Abstract/Free Full Text]
  12. Sharland C, Huggett A, Nielson MS, Friedmann PS. Persistent pruritus after pentastarch infusions in intensive care patients. Anaesthesia 1999; 54: 500–1.[Web of Science][Medline]
 

Response

Joachim Boldt, MD, and Hans-Joachim Priebe, FRCA

Department of Anesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany Department of Anesthesia, University Hospital, Freiburg, Freiburg, Germany

In Response:

We thank Dr Celik for his simulating remarks and would like to answer to his criticisms in detail:

1. In a study of our group using different HES preparations in elderly patients (>60 yr) undergoing major abdominal surgery (2) we found indeed a small increase in some markers of altered kidney function (e.g., {alpha}-1-microglobulin). However, also patients in whom gelatin was given showed similar changes. As gelatin is unlikely to alter kidney function, these changes are most likely due to an extended surgical trauma rather than due to IV administration of HES.

2. The same results were seen in elderly cardiac surgery patients (3) also indicating considerable negative effects of the cardiopulmonary bypass rather than negative effects of modern HES preparations.

3. In the study from Dehne et al. (4), 1000 mL of HES was continuously given over 24 h in critically ill intensive care patients (n = 10)—a rather unusual technique to correct hypovolemia in these patients. A group of patients without volume served as a control (n = 15)—also rather unusual that critically ill patient do not need volume. Significantly more of the HES-treated patients needed hemofiltration due to development of acute renal failure (ARF). Whether these patients were removed from the further study or not remains unclear. Moreover, this was a very small study without power analysis!

4. In the study from Schortgen (5), a HES preparation with high molar substitution (MS) (HES 200/0.62) was used in intensive care patients and compared with a group in whom gelatin was given. Unfortunately, the HES-patients showed higher creatinine levels than gelatin patients already prior to the study. HES patients showed higher creatinine levels during the study period, however, there were no differences between the two groups with regard to the need of hemofiltration/dialysis and outcome. The authors concluded that by using more rapidly degradable HES preparations (with a lower MS) these negative results on kidney function may not have been noticed.

5. This statement remains unclear: "Renal impairment is also seen with high-molecular weight HES preparations used in the United States." The study (6) Dr. Celik cited has the title: "Hydroxyethyl starches does no impair immediate renal function in kidney transplant recipients...".

6. In the retrospective study in cardiac surgery by Winkelmeyer et al. (7), an HES preparation with a very large MW (670 kd) and a very high MS (0.75) was shown to alter kidney function; this is an argument pro the fact that the different HES preparations have to be distinguished—especially slowly degradable HES preparations that show considerable risk to produce kidney dysfunction.

7. It remains unclear what the reported differences in histamine release have to do with possible alterations in kidney function (8).

8. In the study using albumin in patients with spontaneous bacterial peritonitis, one group received albumin, and a control group received no additional volume (9). As expected, the untreated (hypovolemic) control patients developed kidney dysfunction more often; this has nothing to do with beneficial effects of albumin on kidney function! This comparison is not fair.

9. Finally, Dr. Celik has (unfortunately) forgotten to mention a recently published study using a new, third-generation HES preparation (HES 130/0.4) in patients with mild-to-severe renal dysfunction before IV HES administration (1). No negative effects on creatinine clearance were seen with the HES preparation.

Summarizing all studies, it seems to be well established that some older HES preparations (especially with a higher MW and a higher MS) may be associated with alterations in kidney function.

References

  1. Jungheinrich C, Scharpf R, Wargenau M, et al. The pharmacokinetics and tolerability of an intravenous infusion of the new hydroxyethyl starch 130/0.4 (6%, 500 mL) in mild-to-severe renal impairment. Anesth Analg 2002; 95: 544–551.[Abstract/Free Full Text]
  2. Kumle B, Boldt J, Piper S, et al. The influence of different intravascular volume replacement regimens on renal function in the elderly. Anesth Analg 1999; 89: 1124–30.
  3. Boldt J, Brenner T, Lehmann A, et al. Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: comparison of a new starch preparation with gelatin. Intensive Care Med 2003; 29: 763–9.
  4. Dehne MG, Muhling J, Sablotzki A, et al. Effect of hydroxyethyl starch solution on kidney function in surgical intensive care patients. Anästhesiol Intensivmed Notfallmed Schmerzther 1997; 32: 348–54.
  5. Schortgen F, Lacherade JC, Bruneel F, et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 2001; 357: 911–6.
  6. Deman A, Peeters P, Sennesael J. Hydroxyethyl starch does not impair immediate renal function in kidney transplant recipients: a retrospective, multicentre analysis. Nephrol Dial Transplant 1999; 14: 1517–20.
  7. Winkelmayer WC, Glynn RJ, Levin R, Avorn J. Hydroxyethyl starch and change in renal function in patients undergoing coronary artery bypass graft surgery. Kidney Int 2003; 64: 1046–9.
  8. Celik I, Duda D, Stinner B, et al. Early and late histamine release induced by albumin, hetastarch and polygeline: some unexpected findings. Inflamm Res 2003; 52: 408–16.
  9. Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999; 341: 403–9.




This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Celik, I.
Right arrow Articles by Priebe, H.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Celik, I.
Right arrow Articles by Priebe, H.-J.

Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2004 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press