Nephrotoxicity/renal failure after therapy with 90Yttrium- and 177Lutetium-radiolabeled somatostatin analogs in different types of neuroendocrine tumors: a systematic review.

Background/objective: Data regarding the nephrotoxicity of the peptide receptor radionuclide therapy (PRRT) with Yttrium- and Lutetium-radiolabeled somatostatin analogs (RSA) are inconclusive. We aimed to evaluate the short- and long-term nephrotoxicity following PRRT usage in patients with all types of neuroendocrine tumors (NETs).

Methods: A systematic review of observational studies reporting data about nephrotoxicity after treatment with Yttrium and Lutetium RSA was performed. Data on serum creatinine, creatinine clearance, glomerular filtration rate (GFR) and need for renal replacement therapy were compiled. We included patients with progressive, inoperable symptomatic G1, G2 and G3 different types of NETs. After searching in three electronic databases PubMed, Scopus and the Cochrane Library, from 1 January 1978 to November 2018, data were extracted and summarized using a random-effects model.

Results: The final analysis included 34 studies, comprising 5386 participants, enrolling patients with G1, G2, G3 NETs and a follow-up from 12 up to 191 months. Compared with renal function before treatment, measured/estimated glomerular filtration rate (m/eGFR) values changed after PRRT, with a mean annual decrease following PRRT between 2 and 4 mL/min/1.73 m suggesting different grades of nephrotoxicity after PRRT. When compared, Y-RSA and the Y-RSA-Lu-RSA combination are associated with a higher m/eGFR decline compared to Lu-RSA alone.

Conclusions: PRRT can be followed by potentially serious long-term nephrotoxicity, despite kidney protection. The use of the quantified renal function combined with a long follow-up period and personalized dosimetry-based PRRT can reduce nephrotoxicity, in order to use the whole PRRT potential in the management of NETs.