Top

Published in:

Open Access 01-12-2014 | Original research

Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy

Authors: Constantin Lapa, Rudolf A Werner, Christina Bluemel, Katharina Lueckerath, Dirk O Muegge, Alexander Strate, Heribert Haenscheid, Andreas Schirbel, Martin S Allen-Auerbach, Ralph A Bundschuh, Andreas K Buck, Ken Herrmann

Published in: EJNMMI Research | Issue 1/2014

Abstract

Background

Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0).

Methods

In 38 patients, standard activity of ¹⁷⁷Lu-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated.

Results

At 4 h, HK (≥5.0) was present in 94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK.

Increases in K⁺ were significantly correlated with decreases in phosphate (r = −0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of >28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37).

Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK >6.0 (accuracy = 81.6%).

Conclusions

A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining its potential utility for identifying ‘high-risk’ patients prone to PRRT.

Available only for authorised users

Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP, Moss SF, Nilsson O, Rindi G, Salazar R, Ruszniewski P, Sundin A: Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 2008, 9: 61–72.CrossRefPubMed

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: 936–941.CrossRefPubMed

Bergsma H, van Vliet EI, Teunissen JJ, Kam BL, de Herder WW, Peeters RP, Krenning EP, Kwekkeboom DJ: Peptide receptor radionuclide therapy (PRRT) for GEP-NETs. Best Pract Res Clin Gastroenterol 2012, 26: 867–881.CrossRefPubMed

Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, Macke HR, Rochlitz C, Muller-Brand J, Walter MA: Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol 2011, 29: 2416–2423.CrossRefPubMed

Valkema R, Pauwels SA, Kvols LK, Kwekkeboom DJ, Jamar F, de Jong M, Barone R, Walrand S, Kooij PP, Bakker WH, Lasher J, Krenning EP: Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0), Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate. J Nucl Med 2005, 46: 83–91.

Bodei L, Mueller-Brand J, Baum RP, Pavel ME, Horsch D, O’Dorisio MS, O’Dorisio TM, Howe JR, Cremonesi M, Kwekkeboom DJ, Zaknun JJ: The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2013, 40: 800–816.PubMedCentralCrossRefPubMed

de Jong M, Krenning E: New advances in peptide receptor radionuclide therapy. J Nucl Med 2002, 43: 617–620.PubMed

Jamar F, Barone R, Mathieu I, Walrand S, Labar D, Carlier P, de Camps J, Schran H, Chen T, Smith MC, Bouterfa H, Valkema R, Krenning EP, Kvols LK, Pauwels S: 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: 510–518.CrossRefPubMed

Bodei L, Cremonesi M, Grana C, Rocca P, Bartolomei M, Chinol M, Paganelli G: Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004, 31: 1038–1046.CrossRefPubMed

10.

Werner RA, Bluemel C, Allen-Auerbach MS, Higuchi T, Herrmann K: ⁶⁸Gallium- and⁹⁰Yttrium-/¹⁷⁷Lutetium: “theranostic twins” for diagnosis and treatment of NETs. Ann Nucl Med 2014. doi:10.1007/s12149–014–0898–6

11.

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.CrossRefPubMed

12.

Bernard BF, Krenning EP, Breeman WA, Rolleman EJ, Bakker WH, Visser TJ, Macke H, de Jong M: D-lysine reduction of indium-111 octreotide and yttrium-90 octreotide renal uptake. J Nucl Med 1997, 38: 1929–1933.PubMed

13.

Giovacchini G, Nicolas G, Freidank H, Mindt TL, Forrer F: Effect of amino acid infusion on potassium serum levels in neuroendocrine tumour patients treated with targeted radiopeptide therapy. Eur J Nucl Med Mol Imaging 2011, 38: 1675–1682.CrossRefPubMed

14.

Lapa C, Werner RA, Bluemel C, Lückerath K, Schirbel A, Strate A, Buck AK, Herrmann K: Influence of the amount of co-infused amino acids on post-therapeutic potassium levels in peptide receptor radionuclide therapy. EJNMMI Res 2014, 4: 46.PubMedCentralCrossRefPubMed

15.

Hahn K, Franzius C: DGN-Handlungsempfehlung (S1-Leitlinie) Nierenfunktionsszintigraphie mit und ohne Furosemidbelastung bei Kindern und Erwachsenen. AWMF-Registernummer: 031–042. 04/2013.

16.

Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, Schmidt MA, Bugaj JL, de Jong M, Krenning EP: [177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. Eur J Nucl Med 2001, 28: 1319–1325.CrossRefPubMed

17.

Zou KH, O’Malley AJ, Mauri L: Receiver-operating characteristic analysis for evaluating diagnostic tests and predictive models. Circulation 2007, 115: 654–657.CrossRefPubMed

18.

Levinsky NG, Tyson I, Miller RB, Relman AS: The relation between amino acids and potassium in isolated rat muscle. J Clin Invest 1962, 41: 480–487.PubMedCentralCrossRefPubMed

19.

Dickerman HW, Walker WG: Effect of cationic amino acid infusion on potassium metabolism in vivo. Am J Physiol 1964, 206: 403–408.PubMed

20.

Barone R, Pauwels S, De Camps J, Krenning EP, Kvols LK, Smith MC, Bouterfa H, Devuyst O, Jamar F: Metabolic effects of amino acid solutions infused for renal protection during therapy with radiolabelled somatostatin analogues. Nephrol Dial Transplant 2004, 19: 2275–2281.CrossRefPubMed

21.

Massara F, Cagliero E, Bisbocci D, Passarino G, Carta Q, Molinatti GM: The risk of pronounced hyperkalaemia after arginine infusion in the diabetic subject. Diabete Metab 1981, 7: 149–153.PubMed

22.

Esser JP, Krenning EP, Teunissen JJ, Kooij PP, van Gameren AL, Bakker WH, Kwekkeboom DJ: 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: 1346–1351.CrossRefPubMed

Title: Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy
Authors: Constantin Lapa
Rudolf A Werner
Christina Bluemel
Katharina Lueckerath
Dirk O Muegge
Alexander Strate
Heribert Haenscheid
Andreas Schirbel
Martin S Allen-Auerbach
Ralph A Bundschuh
Andreas K Buck
Ken Herrmann
Publication date: 01-12-2014
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2014
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-014-0074-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2014

Insight on automated lesion delineation methods for PET data

Heterogeneity of microsphere distribution in resected liver and tumour tissue following selective intrahepatic radiotherapy

Feasibility of preoperative 125I seed-guided tumoural tracer injection using freehand SPECT for sentinel lymph node mapping in non-palpable breast cancer

Labeling galectin-3 for the assessment of myocardial infarction in rats

A comparison of three 67/68Ga-labelled exendin-4 derivatives for β-cell imaging on the GLP-1 receptor: the influence of the conjugation site of NODAGA as chelator

Optimising the radiolabelling properties of technetium tricarbonyl and His-tagged proteins