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 [(90)Y-DOTA(0),Tyr(3)]octreotide ((90)Y-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 (90)Y-DOTATOC ranging from 7,030 to 35,520 MBq. To inhibit tubular reabsorption of (90)Y-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 (90)Y-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.