Colloids Can Cause Renal Failure

1. Colloids Can Cause Renal Failure MFM James Dept of Anaesthesia University of Cape Town

2. Colloids and ARF Colloids are frequently given in resuscitation A goal of therapy is the maintenance of renal function Are the colloids potentially harmful to the kidney under certain circumstances?

3. Colloids and ARF First description after infusion of Dextran 40 Mailloux et al, N.Engl.J Med., 1967 Matheson et al, Surg.Gynecol.Obstet., 1970 Subsequently described with Gelatin 10% HES 20% mannitol 20% albumin High MS HES

4. Possible Mechanisms Accumulation of low MW fractions in tubules (direct toxicity) Osmotic nephrosis-like lesions (vacuolization of proximal tubular cells) Hyperoncotic renal failure

5. Low MW Fractions Precipitation of particles in tubules Tubular accumulation of particles Tubular obstruction responsive to diuretic therapy Possible tubular uptake and direct toxicity Only described with dextrans

6. Osmotic Nephrosis-Like Lesions Reported with all colloids, including albumin Associated with characteristic tubular lesions Functional significance?

7. Pathology Also shown with Mannitol Hypertonic glucose Cyclosporin A Functional significance questionable Inconsistent relationship to ARF

8. Hyperoncotic Renal Failure Glomerular filtration of hyperoncotic molecules causes hyperviscous urine, stasis and tubular obstruction Chinitz et al, J Lab Clin Med, 1971 Effective filtration pressure depends on the balance of hydrostatic and osmotic pressures:GFR = Kf [(Pcap- Pbow)-(?plas - ?bow)] Moran & Kapsner, NEJM, 1987

9. Hyperoncotic Renal Failure GFR = Kf [(Pcap- Pbow)-(?plas - ?bow)] ?bow = 0 GFR = Kf [(Pcap- Pbow)-?plas] If Pcap is low and ?plas is high, glomerular filtration will cease

10. Hyperoncotic Renal Failure Occurs with all hyperoncotic colloids Inadequate crystalloid administration Occurs in dehydrated patients given large volumes of hyperoncotic solutions Most likely with poorly-filtered, osmotically-active particles

11. Hyperoncotic Renal FailureDextran

12. Hyperoncotic Renal FailureDextran

13. Hyperoncotic Renal FailureAlbumin in Cirrhosis

14. Hyperoncotic Renal FailureGelatin ABF grafting with 200ml blood loss 2L gelatin given for low urine output and to keep CVP > 8mmHg Minimal crystalloid given Postoperatively 20% albumin given Anuric renal failure ? Contribution from gelatin

15. Renal InjuryGelatin The small gelatin molecules are excreted through the glomeruli They form part of the ultrafiltrate and a small portion is reabsorbed whereas the major part is excreted in the urine

16. Morphological findings following gelatin administration Gelatin molecules are excreted through the glomeruli. A small portion of the ultrafiltrate is reabsorbed whereas the major part is excreted in the urine Reabsorption occurs via vacuoles which are surrounded by a simple membrane. The presence of gelatin could be demonstrated by fluorescence

17. ARF and HESAssumptions Renal toxicity of HES is now well recognised Peron et al, Clin Nephrol, 2001 Administration of even low doses of HES causes tubular lesions in patients predisposed to renal insufficiency De Labarthe et al, Am J Med, 2001

18. ARF and HES Systematic review, English, human: Keywords Kidney, kidney function/dysfunction, renal function/dysfunction, volume replacement, HES, dextran, gelatin 12 studies identified 3 articles describing renal injury with HES

19. HES v Gelatin in elderly cardiac surgery patients

20. HES v Gelatin in elderly cardiac surgery patients

21. Renal Function and AAA 62 patients received 6% HES 200/0.62, 6% HES 130/0.4 or GEL for volume Serum urea and creatinine were lower with HES 130/0.4 than GEL at 1, 2 and 5 days after surgery Markers of renal injury lower in HES v GEL HES compared to GEL improved renal function and reduced renal injury

23. What about VISEP? As used in this study, HES was harmful, and its toxicity increased with accumulating doses Brunkhorst et al, New Engl J Med 2008 Volume therapy with RL or 10% HES 200/0.5 Crystalloid usage in HES group not specified

24. VISEP Renal Data

25. Criticisms What you should not do: Use hyperoncotic colloids Use inadequate crystalloid support Use high MS HES in large amounts VISEP Study 10% HES 200/0.5 Crystalloid allocation not specified Very large doses of high MS HES Brunkhorst et al, New Engl J Med 2008

26. Reasonable VISEP Conclusions Hyperoncotic colloid administered in a manner not currently recommended will result in renal dysfunction in the critically ill

27. HES v Albumin in Cardiacs 50 Elderly, low albumin patients for cardiacs Elevated pre-op creatinine 2.9L Alb v 3.0L HES No difference in: Renal function to 3 mth Inflammatory response HES decreased ICAM Boldt et al, Anesth Analg, 2008

28. HES and Renal Failure Observational study of 363 patients: HES 130/0.4 (HES + ) n=168 No HES (HES - ) n=195 Risk of renal dysfunction assessed using RIFLE criteria HES + group more severely ill on admission Boussekey et al., Critical Care, 2010

29. HES and Renal Failure

30. HES and Renal Failure Endotoxic shock induced by Salmonella typhosa infusion to MAP <65 mmHg in 30 adult sheep Resuscitated with balanced crystalloid, isotonic 6 % HES 130/0.4, or hyperoncotic 10 % HES 200/0.5 Study endpoints: Urine output Plasma creatinine Urea concentrations Ertmer et al., Anesthesiology, 2010

31. HES and Renal Failure

32. HES and Renal FailureOverall evidence No evidence that tetrastarch has adverse renal effects in high doses Hyperoncotic colloids may be associated with renal injury Concern remains in sepsis �Potential for increased risk of AKI should be considered when weighing the risks and benefits of HES for volume resuscitation, particularly in septic patients� Dart et al., Cochrane Collaboration, 2010

33. Hyperoncotic Colloids Renal dysfunction: Hyperoncotic colloids [OR: 2.48 (1.2-4.9)] Hyperoncotic albumin [OR: 5.99 (2.7-13.1)] ICU death Hyperoncotic albumin [OR: 2.79 (1.4-5.5)] Schortgen et al, Intens Care Med, 2008

34. Trauma Trial First, randomised, controlled, double blind study of crystalloid v colloid 0.9% saline v HES 130/0.4 in saline End points Fluid volumes for resuscitation GIT dysfunction Renal function James et al, unpublished data, 2009

35. What is the Evidence? Clear evidence that high dose hyperoncotic colloids can cause renal failure Inadequate crystalloid provision is probably a significant risk factor No evidence that colloid molecules per se are nephrotoxic