Abstract

BackgroundAmino acid co-infusion for renal protection in endoradiotherapy (ERT) applied as prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) or peptide receptor radionuclide therapy (PRRT) has been shown to cause severe hyperkalemia. The pathophysiology behind the rapid development of hyperkalemia is not well understood. We hypothesized that the hyperkalemia should be associated with metabolic acidosis.ResultsTwenty-two patients underwent ERT. Prior to the first cycle, excretory kidney function was assessed by mercapto-acetyltriglycine (MAG-3) renal scintigraphy, serum biochemistry, and calculated glomerular filtration rate (eGFR). All patients received co-infusion of the cationic amino acids L-arginine and L-lysine for nephroprotection. Clinical symptoms, electrolytes, and acid-base status were evaluated at baseline and after 4 h.No patient developed any clinically relevant side effects. At baseline, acid base status and electrolytes were normal in all patients. Excretory kidney function was normal or only mildly impaired in all except two patients with stage 3 renal insufficiency. All patients developed hyperkalemia. Base excess and HCO3− were significantly lower after 4 h. In parallel, mean pH dropped from 7.36 to 7.29. There was a weak association between calculated (r = − 0.21) as well as MAG-3-derived GFR (r = − 0.32) and the rise in potassium after 4 h.ConclusionAmino acid co-infusion during ERT leads to severe metabolic acidosis which induces hyperkalemia by potassium hydrogen exchange. This novel finding implies that commercially available bicarbonate solutions might be an easy therapeutic option to correct metabolic acidosis rapidly.

Highlights

  • Amino acid co-infusion for renal protection in endoradiotherapy (ERT) applied as prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) or peptide receptor radionuclide therapy (PRRT) has been shown to cause severe hyperkalemia

  • Side effects of the amino acids (AAs) infusion No clinically relevant side effects as nausea and vomiting, palpitations, or general malaise have been reported by the patients during and after 2.5% Arg/Lys amino acid infusion, and we observed no adverse events (CTCAE grade 3, 4, or 5)

  • Renal function As reduced kidney function is a significant risk factor for the development of hyperkalemia, we first grouped patients according to the Kidney Disease—Improving Global Outcomes (KDIGO) CKD stages [23]

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Summary

Introduction

Amino acid co-infusion for renal protection in endoradiotherapy (ERT) applied as prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) or peptide receptor radionuclide therapy (PRRT) has been shown to cause severe hyperkalemia. Prostatespecific membrane antigen (PSMA)-targeted radioligand therapy (RLT) and peptide receptor radionuclide therapy (PRRT) utilizing radiolabeled peptides are used to control advanced-stage prostate [1] and neuroendocrine cancer [2, 3]. PRRT is used for glomus tumors and Therapeutic agents in current use for PSMA-targeted RLT and PPRT exhibit high renal excretion rate [8, 9]. Retention at the proximal tubule causes a high effective dose of radiation to the kidneys; there is a need for inhibiting renal uptake of labeled peptides to limit the amount of

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