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Custodiol® HTK Solution is intended for perfusion and flushing of donor liver, kidney, pancreas (and heart) prior to removal from the donor for preserving these organs during hypothermic storage and transport to the recipient.

It is based on the principal of inactivating organ function by withdrawal of extracellular sodium and calcium, together with intense buffering of the extracellular space by means of histidine/histidine HCI, so as to prolong the period for which the organs will tolerate interruption of blood and oxygen.

  • Low Viscosity(2)
  • Low Potassium content safe for systemic absorption(2)
  • Low Sodiurn(3)
  • No Starch
  • Buffered with histidine and histidine HCI
  • Doubles buffering capacity in transplanted organs which moderates drop pH(4)
  • Protects against edema(4)
  • Lower Biliary cornplications(5)(8)
  • No Flush needed(1)

 

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EXTENDED CRITERIA DONORS

In a study comparing HTK and U of Win a large number of SCO and ECO livers, the authors concluded that HTK and U of Ware not clinically distinguishable in the large sample of liver transplants. However, HTK may be protective against biliary complications. Kaplan-Meier graft survival curves failed to demonstrate a significant difference in SCO or ECO livers.(7)

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A recent study concluded that lschemic-type biliary lesions (ITBL) account for a major part of patients’ morbidity and mortality after orthotopic liver transplantation (OLT). This study retrospectively evaluated 1843 patlents.(8)

Organs that were perfused with University of Wisconsin (U of W) solution developed ITBL significantly more often than Histidine-Tryptophane-Ketogluterate (HTK) perfused organs (P=0.036).(8)

The authors of this study mentioned that the clinical consequences of this study for their institution have been the strict limitation of CIT to

In a meta-analysis and systematic review on the effect of preservation solutions for liver transplant, the authors concluded there was no good evidence of any difference in outcomes when comparing HTK and either University of Wisconsin solution or Celsior.(9)

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In a study comparing HTK and U of W in Renal Transplantation, the authors concluded HTK demonstrated similar efficacy to U of Win terms of patient and graft survival.(#10)HTK was associated with a significant risk reduction on the incidence of DGF

  • Graft survival did not significantly differ by preservation solution but in living donor patients, HTK showed a trend toward improved long-term graft survival over U of W solution

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In a study looking at cost effectiveness of preservation solutions in live donor kidneys, it was shown that HTK is superior to LR for preventing DGF, HTK and U of Ware more cost effective than LR and LRD in transplantation. (11)

In a study by Argarwal et at., is was found that HTK is not inferior to U of W (as previously suggested by other authors) and may in fact be better protection for the prevention of delayed graft function compared to U of W solution.(12)

NON LIVING DONOR DATA

In a randomized multi-center study on kidney graft preservation comparing HTK with U of W and Euro Collins, the authors concluded HTK is comparable to U of W in its preservative abilities.(13)

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The multivariate analysis of the U of W-HTK study showed that the kind of preservation solution used was not associated with INF. But four other factors were indeed associated with INF: donor age, donor cause of death, re-transplantation and cold ischemic period(13)

KAPLAIN-MEYER KIDNEY ALLOGRAFT

In a study comparing HTK and U of Win Renal Transplantation, the authors concluded HTK demonstrated similar efficacy to U of Win terms of patient and graft survival.(10)

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A recent study prospectively evaluated early graft function in clinical pancreas transplantation after organ perfusion with HTK versus U of W. This prospective, randomized study, in concordance with the findings of previous retrospective comparisons of pancreas perfusion with HTK versus U of W solution demonstrated equally good patient and graft survival for both preservation fluids. HTK solution appears to be equally suitable as U of W solution for in situ perfusion and organ preservation in clinical pancreas transplantation.(14)

The study was designed as a phase Ill study for Germany.(14)

Normal endocrine function (no need for exogenous insulin) for patients with organs perfused with HTK (n = 27) versus U of W (n = 41) solution during the first 6 months after pancreas transplantation (mo, months).

PANCREAS TRANSPLANTATION USING HTK PRESERVATION: IS IT A CAUTIONARY TALE?(15)

This study looks at pancreas transplant outcomes. The authors performed 115 PTXs (simultaneous kidney PTX (SKPTs) and 28 solitary PTX’s (SPTs) in 114 patients between July 2003 and September 2008.(15)

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A recent study compared the effectiveness of HTK and U of W in the preservation of human pancreata intended for islet isolation. The authors concluded HTK and U of W possess equal capacity to prevent cellular edema throughout the pancreas procurement and isolation process.(16)

The quality of pancreas flush and preservation is one of the most important determining factors for the successful grafting of both whole pancreata and isolated islets.(16)

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Islet purity distribution across purification fractions. The number of isolations analyzed was 95 and 157 for HTK and U of W, respectively. Data was expressed as percentages and adjusted for age, sex, BMI, CIT and enzyme. Sample size ranged from 167-249 across fractions. Statistical significance was set at p<0.01.

The distribution of islet purity across fractions also served as an indicator of purification outcome and an indirect measurement of cellular edema. Within the top fraction (>69%), the islet purity distribution was similar between the HTK and U of W groups. However within the middle fraction (40-69%), a significantly higher purity was observed in fractions 6 and 7 if the HTK group.(16)

 

REFERENCES

1) Custodiol HTK Solution Pl available at http://www.custodiol.com/hansjb/prescribing-info/

2) Erhard J, Lange R, Scherer R, et al. Comparison of histidinetryptophan-ketogluterate (HTK) solution versus University of Wisconsin (U of W) solution for organ preservation in human liver transplantation. A prospective, randomized study. Transplant Int. 1994; 7:177-181

3) Fridell JA, Mangus RS, Teeter AJ. Clinical experience with histidinetryptophan-ketogluterate solution in abdominal organ preservation; a review of recent literature. Clin Transplant 2008 DOI: 10.1111/j.1399- 0012.2008.00958.

4) Gebhard MM, Kirlum HJ, Schlegel C. Organ preservation with

the solution HTK. In: Hess UJ, de Hemptinne B, eds. Organ Preservation with HTK and U of W Solution: Update on Clinical Use and Experimental Studies. Lengerich, Germany: Pabst Science Publishers; 1999:75-87

5) Welling TH, Heidt DG, Englesbe MJ, et al., Biliary complications following liver transplantation in the model for end-stage liver disease era: effect of donor, recipient and technical factors. Liver Transpl. 2008 14:73-80

6) Ringe B, Braun F, Moritz M, Zeldin G, Soriano H, Meyers W. Safety and efficacy of living donor liver preservation with HTK solution. Transplant Proc. 2005; 37:316-319.

7) Mangus RS, Fridell JA, Vianna RM et al. Comparison of histidinetryptophan-ketogluterate solution and University of Wisconsin in Extended Criteria Liver Donors. Liver Transplantation 2008 14:365- 373

8) Heidenhein C, Pratschke J, Puhl G., et al. Incidence of and risk factors for ischemic-type biliary lesions following orthotopic liver transplantation. Transplant Intl. 2009 ISSN 0934-0874

9) O’Callaghan JM, Morgan RD, Knight SR, et al., The effect of preservation solutions for storage of liver allografts on transplant outcomes. A systematic review and meta-analysis. Annals of Surgery 2014:46-55

10) Lynch RJ, Kubus J, Chenault RH, et al., Comparison of histidinetryptophan-ketogluterate and University of Wisconsin preservation in renal transplantation. American Journal of Transplantation. 2008;8:567-573

11) Rofaiel G., Bakthavatsalam R., Dick A., et al., HTK and U of Ware more efficacious and cost effective than LR for the preservation of live donor kidneys. ATC Annual Meeting 2012 Poster Session, Kidney Transplantation

12) Argawal A, Murdock P, Fridell JA. Comparison of histidinetryptophan-ketogluterate (HTK) solution and University of Wisconsin in prolonged cold preservation of kidney allografts. Transplantation. 2006;81 -480-482

13) deBoer J, DeMeester J, Smits, JMA et al., Eurotransplant randomized multicenter kidney graft preservation study comparing HTK with U of Wand Euro-Collins. Transplant Int 199912:447-453

14) Schneeberger S, Biebl M, Steurer W, et. Al., A prospective randomized multicenter trial comparing histidine-tryptophanketogluterate versus University of Wisconsin perfusion solution in clinical pancreas transplantation. Transplant Int. 2008 ISSN 0934- 0874

15) Reddy KS, Moss A, Mekeel Ket al., Pancreas Transplantation using HTK preservative: Is it a cautionary tale? ATC 2009 Poster Session June 1, 2009 Exhibit Hall C

16) Paushter DH, Meirigeng Q, Danielson KK et al., Histidinetryptophan-ketogluterate and University of Wisconsin solution demonstrated equal effectiveness in the preservation of human pancreata intended for islet isolation: A large scale, single-center experience. Cell Transplantation 2013 Vol 22 pp 1113-1121

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