Lutetium-177 PSMA-617 (vipivotide)

PSMA is also expressed on the proximal renal tubular brush border, and filtered ligand is reabsorbed there, so radiation is delivered to the proximal tubule, raising the theoretical risk of chronic radiation nephropathy. Salivary and lacrimal glands likewise concentrate the ligand, producing the prominent xerostomia/dry-eye toxicity. Acute tubular injury can also be hemodynamic if pelvic disease causes obstruction or dehydration.

Renal injury is typically a mild, gradual eGFR decline; the clinically prominent toxicities are xerostomia and dry eyes plus hematologic effects (anemia, thrombocytopenia). A rising creatinine should prompt evaluation for obstructive uropathy from pelvic/nodal disease.

Largely supportive: hydrate, relieve obstruction, and hold/reduce for grade >=3 renal or marrow toxicity. Manage xerostomia symptomatically. Monitor and replace electrolytes as needed.Lesion-level management framework

Standard 7.4 GBq IV every 6 weeks for up to 6 cycles. No simple CrCl-based table; the same ~23 Gy renal radiation-tolerance principle applies (renal dose ~0.4-0.55 Gy/GBq in dosimetry series). Hold/reduce for grade >=3 renal or hematologic toxicity; caution with significantly impaired baseline GFR.

Dialysis does not treat the toxicity (a structural radiation effect, not a removable drug), but hemodialysis-dependent patients CAN be treated — the earlier 'not a candidate' stance is outdated. One hemodialysis patient received all 6 Lu-177 PSMA-617 cycles with dialysis during each and a strong PSA response (298 to 7.1 ng/mL); another completed 5 cycles of PSMA-I&T at the standard 7.4 GBq activity. Dialysis is scheduled after the dose — within about 24 h across the reported series, with a second session near 72 h in one report — to take off the renally-excreted radioligand, with dialysate collected and handled as radioactive waste and measured staff exposure in that report low (2-19 microSv accumulated). Removal is real but partial: blood activity fell 32% over a 3 h session and then partly rebounded, activity already bound in tumor and organs is beyond reach, and bone-marrow dose still ran about twice the non-dialysis literature. Radiation-nephropathy risk is moot in an already-failed kidney; the real issues are blood/marrow dose from slowed clearance and radiation-safety logistics.

Distinguish drug-related radiation effect from obstructive uropathy (hydronephrosis on imaging — common in pelvic prostate cancer), prior platinum/taxane tubular injury, and dehydration. Exclude obstruction before attributing AKI to the radioligand.