Renal protection with amino acid co-infusion

Radiolabelled peptides such as DOTATATE are filtered by the kidney and partly reabsorbed in the proximal tubule, where they can be retained long enough to deliver a clinically significant radiation dose; the kidney is the dose-limiting organ for peptide receptor radionuclide therapy. Co-infusing positively charged amino acids, most commonly a mixture of L-lysine and L-arginine, competitively blocks this tubular reabsorption. The joint IAEA/EANM/SNMMI practical guidance on PRRT describes protocols using 25 g lysine plus 25 g arginine (a 50 g total "cocktail") diluted in 1-2 litres of normal saline and infused over about 4 hours, started 30-60 minutes before the radiopeptide and continued for at least 3-4 hours afterwards; some centres extend protection over 2-3 days post-therapy for additional renal sparing.

Published reductions in renal absorbed dose from amino acid co-infusion range from roughly 9% to 65% depending on amino acid dose, infusion duration, and how long protection is continued after therapy, with a commonly cited average reduction of around 40%. Higher lysine doses (for example 75 g) reduce renal uptake further but cause more side effects such as nausea and vomiting, so 25 g lysine plus 25 g arginine is regarded as the standard trade-off. Hyperkalaemia, nausea and vomiting are the main side effects of the amino acid infusion itself, and hyperosmotic solutions should be avoided in patients with cardiac insufficiency because of the risk of volume overload and electrolyte disturbance.

Despite renal protection, long-term creatinine clearance loss of roughly 3-4% per year has been reported after 177Lu-DOTATATE (compared with a steeper roughly 7% per year after the older 90Y-DOTATOC), and PRRT is generally avoided in patients with a glomerular filtration rate below 30-40 mL/min. A large single-institution retrospective series of over 1,200 patients receiving amino acid-protected PRRT found no clear evidence of long-term nephrotoxicity, though prospective, randomised confirmation across centres is limited. Alternatives such as arginine-only infusion or Gelofusine/succinylated gelatin, and newer approaches such as para-aminohippurate (PAH) co-infusion, are being studied as ways to reduce side effects while preserving nephroprotection.