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Effect of amino acid infusion on potassium serum levels in neuroendocrine tumour patients treated with targeted radiopeptide therapy

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Abstract

Purpose

Administration of positively charged amino acids has been introduced to reduce the nephrotoxicity of targeted radiopeptide therapy (TRT). However, the amino acid solution may have side effects, including hyperkalaemia. The aim of this study was to evaluate the frequency and the magnitude of hyperkalaemia in neuroendocrine tumour (NET) patients undergoing TRT.

Methods

Enrolled in the study were 31 patients with NET eligible for TRT with [90Y-DOTA(0),Tyr(3)]octreotide (90Y-DOTATOC). Their mean age was 54 ± 14 years. Of these 31 patients, 21 (67%) were referred for the first treatment cycle, while 10 (33%) were referred for a subsequent therapy cycle. Patients were treated with therapeutic doses of 90Y-DOTATOC ranging from 7,030 to 35,520 MBq. To inhibit tubular reabsorption of 90Y-DOTATOC, 1 l of physiological saline solution containing 25 g of arginine hydrochloride and 25 g of lysine hydrochloride was given over 4 h starting 1 h before 90Y-DOTATOC injection. All patients underwent a standard biochemical blood analysis at baseline, and 4 h and 24 h after the beginning of the amino acid infusion.

Results

ANOVA repeated measures showed a significant overall effect on K+ levels over time (F = 118.2, df = 2, P < 0.0001). Mean serum levels of K+ were 4.00 ± 0.33 mmol/l at baseline, 5.47 ± 0.57 mmol/l at 4 h, and 4.38 ± 0.63 mmol/l at 24 h after the beginning of the infusion. Post-hoc analysis showed that K+ levels at 4 h were significantly (P < 0.05) higher than at baseline. K+ levels at 24 h were significantly (P < 0.05) lower than at 4 h but they were still significantly (P < 0.05) higher than K+ levels at baseline. On a subject-by-subject basis, none of the 31 patients had increased K+ levels at baseline. At 4 h, 24 of the 31 patients (77%) had K+ levels above the normal range, and 6 patients (19%) experienced severe hyperkalaemia (K+ ≥ 6 mmol/l). All patients with increased K+ levels were clinically asymptomatic. At 24 h, only 4 patients (13%) had increased K+ serum levels. The magnitude of the increase in K+ levels between baseline and 4 h was relatively homogeneous over the whole group (1.41 ± 0.50 mmol/l) and it was not related (linear regression, P>0.05) to baseline K+ levels. Intravenous administration of 40 mg furosemide 1 h after the beginning of the amino acid infusion did not have a significant effect on K+ levels (P>0.05). No clinical characteristic was predictive for the increase in K+ levels (chi-squared test, P > 0.05).

Conclusion

Hyperkalaemia is a frequent, potentially life-threatening side effect of basic amino acid infusion during TRT. K+ levels 4 h after the beginning of the infusion should be monitored in patients at risk of complications, such as those with heart disease and those with risk factors for nephrotoxicity.

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References

  1. Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61–72.

    Article  PubMed  CAS  Google Scholar 

  2. Waser B, Tamma ML, Cescato R, Maecke HR, Reubi JC. Highly efficient in vivo agonist-induced internalization of sst2 receptors in somatostatin target tissues. J Nucl Med. 2009;50:936–41.

    Article  PubMed  CAS  Google Scholar 

  3. Esser JP, Krenning EP, Teunissen JJ, Kooij PP, van Gameren AL, Bakker WH, et al. Comparison of [(177)Lu-DOTA(0),Tyr(3)]octreotate and [(177)Lu-DOTA(0),Tyr(3)]octreotide: which peptide is preferable for PRRT? Eur J Nucl Med Mol Imaging. 2006;33:1346–51.

    Article  PubMed  CAS  Google Scholar 

  4. Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging. 2008;35:1847–56.

    Article  PubMed  CAS  Google Scholar 

  5. Kwekkeboom DJ, Mueller-Brand J, Paganelli G, Anthony LB, Pauwels S, Kvols LK, et al. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med. 2005;46:62S–6.

    PubMed  CAS  Google Scholar 

  6. Forrer F, Waldherr C, Maecke HR, Mueller-Brand J. Targeted radionuclide therapy with 90Y-DOTATOC in patients with neuroendocrine tumors. Anticancer Res. 2006;26:703–7.

    PubMed  CAS  Google Scholar 

  7. de Jong M, Barone R, Krenning E, Bernard B, Melis M, Visser T, et al. Megalin is essential for renal proximal tubule reabsorption of (111)In-DTPA-octreotide. J Nucl Med. 2005;46:1696–700.

    PubMed  Google Scholar 

  8. Mogensen CE, Sølling. Studies on renal tubular protein reabsorption: partial and near complete inhibition by certain amino acids. Scand J Clin Lab Invest. 1977;37:477–86.

    Article  PubMed  CAS  Google Scholar 

  9. Behr TM, Goldenberg DM, Becker W. Reducing the renal uptake of radiolabeled antibody fragments and peptides for diagnosis and therapy: present status, future prospects and limitations. Eur J Nucl Med. 1998;25:201–12.

    Article  PubMed  CAS  Google Scholar 

  10. Barone R, Pauwels S, De Camps J, Krenning EP, Kvols LK, Smith MC, et al. Metabolic effects of amino acid solutions infused for renal protection during therapy with radiolabelled somatostatin analogues. Nephrol Dial Transplant. 2004;19:2275–81.

    Article  PubMed  CAS  Google Scholar 

  11. Bodei L, Cremonesi M, Zoboli S, Grana C, Bartolomei M, Rocca P, et al. Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study. Eur J Nucl Med Mol Imaging. 2003;30:207–16.

    Article  PubMed  CAS  Google Scholar 

  12. Rolleman EJ, Valkema R, de Jong M, Kooij PP, Krenning EP. Safe and effective inhibition of renal uptake of radiolabelled octreotide by a combination of lysine and arginine. Eur J Nucl Med Mol Imaging. 2003;30:9–15.

    Article  PubMed  CAS  Google Scholar 

  13. Rolleman EJ, Melis M, Valkema R, Boerman OC, Krenning EP, de Jong M. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues. Eur J Nucl Med Mol Imaging. 2010;37:1018–31.

    Article  PubMed  Google Scholar 

  14. Bernard BF, Krenning EP, Breeman WA, Rolleman EJ, Bakker WH, Visser TJ, et al. D-lysine reduction of indium-111 octreotide and yttrium-90 octreotide renal uptake. J Nucl Med. 1997;38:1929–33.

    PubMed  CAS  Google Scholar 

  15. Bushinsky DA, Gennari FJ. Life-threatening hyperkalemia induced by arginine. Ann Intern Med. 1978;89:632–4.

    PubMed  CAS  Google Scholar 

  16. Dursun I, Sahin M. Difficulties in maintaining potassium homeostasis in patients with heart failure. Clin Cardiol. 2006;29:388–92.

    Article  PubMed  Google Scholar 

  17. Weiner ID, Wingo CS. Hyperkalemia: a potential silent killer. J Am Soc Nephrol. 1998;9:1535–43.

    PubMed  CAS  Google Scholar 

  18. Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med. 2002;43:610–6.

    PubMed  CAS  Google Scholar 

  19. Forrer F, Uusijarvi H, Waldherr C, Cremonesi M, Bernhardt P, Mueller-Brand J, et al. A comparison of (111)In-DOTATOC and (111)In-DOTATATE: biodistribution and dosimetry in the same patients with metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2004;31:1257–62.

    Article  PubMed  CAS  Google Scholar 

  20. Brater DC, Fox WR, Chennavasin P. Electrolyte excretion patterns. Intravenous and oral doses of bumetanide compared to furosemide. J Clin Pharmacol. 1981;21:599–603.

    PubMed  CAS  Google Scholar 

  21. Valentin J (ed). P103: The 2007 Recommendations of the International Commission on Radiological Protection. Ann ICRP 2008;37(2–4):1–332.

  22. Ponce SP, Jennings AE, Madias NE, Harrington JT. Drug-induced hyperkalemia. Medicine (Baltimore). 1985;64:357–70.

    CAS  Google Scholar 

  23. Sica DA, Gehr TW, Yancy C. Hyperkalemia, congestive heart failure, and aldosterone receptor antagonism. Congest Heart Fail. 2003;9:224–9.

    Article  PubMed  CAS  Google Scholar 

  24. Levinsky NG, Tyson I, Miller RB, Relman AS. The relation between amino acids and potassium in isolated rat muscle. J Clin Invest. 1962;41:480–7.

    Article  PubMed  CAS  Google Scholar 

  25. Dickerman HW, Walker WG. Effect of cationic amino acid infusion on potassium metabolism in vivo. Am J Physiol. 1964;206:403–8.

    PubMed  CAS  Google Scholar 

  26. Merimee TJ, Lillicrap DA, Rabinowitz D. Effect of arginine on serum-levels of human growth-hormone. Lancet. 1965;2:668–70.

    Article  PubMed  CAS  Google Scholar 

  27. Nyirenda MJ, Tang JI, Padfield PL, Seckl JR. Hyperkalaemia. BMJ. 2009;339:b4114.

    Article  PubMed  Google Scholar 

  28. Obialo CI, Ofili EO, Mirza T. Hyperkalemia in congestive heart failure patients aged 63 to 85 years with subclinical renal disease. Am J Cardiol. 2002;90:663–5.

    Article  PubMed  CAS  Google Scholar 

  29. Vereijken TL, Bellersen L, Groenewoud JM, Knubben L, Baltussen L, Kramers C. Risk calculation for hyperkalaemia in heart failure patients. Neth J Med. 2007;65:208–11.

    PubMed  CAS  Google Scholar 

  30. Reardon LC, Macpherson DS. Hyperkalemia in outpatients using angiotensin-converting enzyme inhibitors. How much should we worry? Arch Intern Med. 1998;158:26–32.

    Article  PubMed  CAS  Google Scholar 

  31. Herman E, Rado J. Fatal hyperkalemic paralysis associated with spironalactone. Observation on a patient with severe renal disease and refractory edema. Arch Neurol. 1966;15:74–7.

    PubMed  CAS  Google Scholar 

  32. Desai AS. Hyperkalemia in patients with heart failure: incidence, prevalence, and management. Curr Heart Fail Rep. 2009;6:272–80.

    Article  PubMed  CAS  Google Scholar 

  33. Jamar F, Barone R, Mathieu I, Walrand S, Labar D, Carlier P, et al. 86Y-DOTA0)-D-Phe1-Tyr3-octreotide (SMT487) – a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med Mol Imaging. 2003;30:510–8.

    Article  PubMed  CAS  Google Scholar 

  34. Cox M, Sterns RH, Singer I. The defense against hyperkalemia: the roles of insulin and aldosterone. N Engl J Med. 1978;299:525–32.

    Article  PubMed  CAS  Google Scholar 

  35. Kim HJ, Han SW. Therapeutic approach to hyperkalemia. Nephron. 2002;92 Suppl 1:33–40.

    Article  PubMed  CAS  Google Scholar 

  36. Vegt E, Wetzels JF, Russel FG, Masereeuw R, Boerman OC, van Eerd JE, et al. Renal uptake of radiolabeled octreotide in human subjects is efficiently inhibited by succinylated gelatin. J Nucl Med. 2006;47:432–6.

    PubMed  CAS  Google Scholar 

  37. van Eerd JE, Vegt E, Wetzels JF, Russel FG, Masereeuw R, Corstens FH, et al. Gelatin-based plasma expander effectively reduces renal uptake of 111In-octreotide in mice and rats. J Nucl Med. 2006;47:528–33.

    PubMed  Google Scholar 

  38. Vegt E, van Eerd JE, Eek A, Oyen WJ, Wetzels JF, de Jong M, et al. Reducing renal uptake of radiolabeled peptides using albumin fragments. J Nucl Med. 2008;49:1506–11.

    Article  PubMed  CAS  Google Scholar 

  39. Gielkens HA, Lamers CB, Masclee AA. Effect of amino acids on lower esophageal sphincter characteristics and gastroesophageal reflux in humans. Dig Dis Sci. 1998;43:840–6.

    Article  PubMed  CAS  Google Scholar 

  40. Hertz P, Richardson JA. Arginine-induced hyperkalemia in renal failure patients. Arch Intern Med. 1972;130:778–80.

    Article  PubMed  CAS  Google Scholar 

  41. Bodei L, Cremonesi M, Grana C, Rocca P, Bartolomei M, Chinol M, et al. Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2004;31:1038–46.

    Article  PubMed  CAS  Google Scholar 

  42. de Jong M, Rolleman EJ, Bernard BF, Visser TJ, Bakker WH, Breeman WA, et al. Inhibition of renal uptake of indium-111-DTPA-octreotide in vivo. J Nucl Med. 1996;37:1388–92.

    PubMed  Google Scholar 

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Acknowledgments

We would like to thank Martin Speiser for clinical support, Fausta Chiaverio for administrative support, and Sandra Vomstein and Daniela Biondo for processing the radioactive blood samples.

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Radiology and Nuclear Medicine, Division of Endocrine Diagnostics and Radionuclide Therapy, University Hospital Basel, 4031, Basel, Switzerland

    Giampiero Giovacchini, Guillaume Nicolas & Flavio Forrer

  2. Laboratory Medicine, University Hospital Basel, Basel, Switzerland

    Heike Freidank

  3. Division of Radiological Chemistry, University Hospital Basel, Basel, Switzerland

    Thomas L. Mindt

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  1. Giampiero Giovacchini
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  2. Guillaume Nicolas
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Correspondence to Giampiero Giovacchini.

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Giovacchini, G., Nicolas, G., Freidank, H. et al. Effect of amino acid infusion on potassium serum levels in neuroendocrine tumour patients treated with targeted radiopeptide therapy. Eur J Nucl Med Mol Imaging 38, 1675–1682 (2011). https://doi.org/10.1007/s00259-011-1826-9

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  • DOI: https://doi.org/10.1007/s00259-011-1826-9

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