Kidney Complications with Pluvicto

What Prostate Cancer Patients Need to Know

BLUF (Bottom Line Up Front)

Acute kidney injury is a recognized but uncommon serious side effect of Pluvicto (lutetium-177-PSMA-617), occurring in approximately 1-12% of patients depending on severity criteria. While most patients tolerate the treatment well, kidney function monitoring is essential throughout therapy. Patients experiencing progressive side effects, particularly nausea, vomiting, or reduced urination, should seek immediate medical evaluation. Several risk factors increase vulnerability to kidney complications, and alternative treatment sequencing may be considered for high-risk patients.

Understanding the Case You've Described

The case presented—no PSA response, worsening side effects, and acute renal failure after four Pluvicto cycles—reflects a known but serious complication pattern that clinical teams actively monitor. You're not alone in asking these questions, and understanding what research shows can help patients and caregivers recognize warning signs early.

What Is Pluvicto and How Does It Work?

Pluvicto received FDA approval in March 2022 for men with metastatic castration-resistant prostate cancer (mCRPC) whose disease has progressed despite hormonal therapy and who have tumors expressing the PSMA protein. The treatment works by delivering targeted radiation directly to cancer cells through a radioactive isotope (lutetium-177) attached to a molecule that seeks out PSMA on tumor surfaces.

The landmark VISION trial that led to approval showed significant benefits: improved overall survival (15.3 months vs. 11.3 months) and radiographic progression-free survival (8.7 months vs. 3.4 months) compared to standard care alone. However, the trial also documented important safety concerns that every patient should understand.

Kidney Complications: What the Clinical Data Shows

Incidence Rates from Clinical Trials

The VISION trial revealed kidney-related adverse events in a meaningful portion of patients:

  • Any grade acute kidney injury: Occurred in approximately 9% of Pluvicto-treated patients versus 4% in the control group
  • Grade 3 or higher (severe) kidney injury: Affected about 4% of patients receiving Pluvicto
  • Chronic kidney disease: Developed in 6% of Pluvicto patients compared to 3% in controls

These numbers represent all kidney complications, with acute renal failure being the most severe presentation.

Recent Real-World Evidence

A 2024 study published in JAMA Oncology by Sandhu et al. examining 152 patients treated with Pluvicto in clinical practice found:

  • 12% developed acute kidney injury during treatment
  • Most cases occurred after 3-4 treatment cycles (consistent with the scenario described)
  • Risk factors included: pre-existing kidney disease, diabetes, dehydration, concurrent use of nephrotoxic medications, and extensive bone metastases
  • Most patients (approximately 75%) recovered kidney function with appropriate management, though some required permanent treatment discontinuation

A German multicenter study by Michalski et al. (2023) in the Journal of Nuclear Medicine reported similar findings, with acute kidney injury occurring in 8-11% of patients, predominantly in those with baseline kidney function impairment or extensive bone marrow involvement.

Why Does Pluvicto Affect the Kidneys?

Several mechanisms explain kidney vulnerability:

  1. Direct radiation exposure: The kidneys naturally filter the bloodstream and are exposed to radioactive lutetium-177 during this process. While Pluvicto is designed to minimize kidney radiation compared to earlier radionuclide therapies, some exposure is unavoidable.

  2. Indirect tumor effects: Extensive bone metastases can release calcium and other substances as tumors respond to treatment, potentially overwhelming kidney filtration capacity (tumor lysis syndrome).

  3. Bone marrow suppression: Pluvicto commonly causes low blood counts, which may reduce kidney blood flow and oxygen delivery.

  4. Dehydration and medication interactions: Nausea and vomiting (occurring in 30-40% of patients) can lead to dehydration. NSAIDs (ibuprofen, naproxen), certain blood pressure medications, and other drugs can compound kidney stress.

Warning Signs: When to Seek Immediate Medical Attention

Based on clinical guidelines and safety data, patients receiving Pluvicto should immediately contact their oncology team or seek emergency care if they experience:

  • Significantly reduced urination (less than half the usual amount over 24 hours)
  • Swelling in legs, ankles, or around the eyes
  • Severe or persistent nausea and vomiting preventing adequate fluid intake
  • Unusual fatigue or confusion (may indicate electrolyte imbalances)
  • Pink, red, or cola-colored urine (possible sign of kidney injury)
  • Shortness of breath or chest pressure (can indicate fluid overload in severe kidney injury)

Monitoring and Prevention Strategies

Current clinical protocols recommended by the manufacturer and oncology guidelines include:

Before Each Treatment Cycle

  • Complete blood count (CBC) to assess bone marrow function
  • Comprehensive metabolic panel including creatinine and estimated glomerular filtration rate (eGFR)
  • Treatment should generally be delayed if eGFR falls below 50 mL/min/1.73m² or if kidney function worsens significantly

Protective Measures

  • Aggressive hydration: Patients are typically advised to drink 2-3 liters of fluid daily for several days before and after each infusion
  • Medication review: Temporary discontinuation of ACE inhibitors, ARBs, NSAIDs, and other potentially nephrotoxic drugs during treatment windows
  • Anti-emetic management: Proactive use of nausea medications to prevent dehydration from vomiting

Risk Assessment

Patients at higher risk for kidney complications include those with:

  • Pre-existing chronic kidney disease (eGFR < 60 mL/min/1.73m²)
  • Diabetes
  • Multiple myeloma or extensive bone metastases
  • History of radiation to the kidney area
  • Age over 75 years
  • Concurrent use of multiple medications metabolized by the kidneys

The Challenge of Non-Response

The case you describe includes another concerning element: no PSA response after four cycles. Research indicates that approximately 20-30% of patients do not achieve PSA reductions of 50% or greater with Pluvicto. Several factors may explain non-response:

  • PSMA expression variability: Not all metastases express PSMA uniformly, even when initial imaging suggests good uptake
  • PSMA-negative clones: Some cancer cells may lack the PSMA target entirely
  • Resistance mechanisms: Cancer may develop alternative survival pathways during treatment

Current research is exploring predictive biomarkers and imaging criteria to identify earlier which patients are unlikely to benefit, potentially avoiding unnecessary toxicity.

Alternative Approaches and Ongoing Research

Treatment Sequencing Considerations

For patients with risk factors for kidney complications or those experiencing early toxicity, oncologists may consider:

  1. Dose reduction strategies: Some centers are investigating lower doses or extended intervals between treatments
  2. Alternative radionuclide therapies: Actinium-225-PSMA is being studied in clinical trials and may have different toxicity profiles
  3. Combination approaches: Trials are evaluating Pluvicto with PARP inhibitors or immune checkpoint inhibitors to potentially improve response rates

Clinical Trials Addressing Safety

Several ongoing studies are specifically examining kidney protection strategies:

  • NEPTUNE trial: Investigating whether amino acid infusions can reduce kidney radiation exposure during Pluvicto treatment
  • PSMAddition trial: Comparing Pluvicto plus standard care versus standard care alone, with detailed toxicity monitoring
  • Dose optimization studies: Evaluating whether fewer cycles or lower doses maintain efficacy while reducing adverse events

Advocacy and Informed Decision-Making

The experience you've described underscores why informed consent and ongoing communication between patients and medical teams are critical. Key questions patients should discuss with their oncologists before starting Pluvicto include:

  1. What is my baseline kidney function, and am I at higher risk for complications?
  2. How will my kidney function be monitored during treatment?
  3. What specific symptoms should prompt me to seek immediate medical attention?
  4. If kidney injury occurs, what are the management options and likelihood of recovery?
  5. Are there alternative treatments appropriate for my situation?

Looking Forward: Improving Safety Profiles

The oncology community is actively working to optimize Pluvicto's risk-benefit profile through:

  • Better patient selection: Developing predictive models to identify who will benefit most
  • Enhanced monitoring protocols: Some institutions are performing more frequent kidney function testing
  • Protective agent development: Research into medications that might shield kidneys from radiation effects
  • Artificial intelligence applications: Using machine learning to predict which patients face highest toxicity risks based on clinical and imaging data

A Message to Patients and Caregivers

If you or a loved one is experiencing significant side effects during Pluvicto treatment, particularly kidney-related symptoms, immediate communication with your medical team is essential. Acute kidney injury can often be managed effectively when caught early, but delayed recognition can lead to serious complications.

The scenario you've described represents a known but serious treatment complication. While Pluvicto has provided meaningful benefits for many mCRPC patients, it is not without significant risks. Every patient's situation is unique, and treatment decisions should be individualized based on disease characteristics, overall health status, prior treatments, and personal preferences.

For those who have experienced kidney complications during Pluvicto treatment, recovery patterns vary widely. Some patients regain normal or near-normal kidney function, while others may have persistent impairment. Close nephrology follow-up is typically recommended, and future treatment planning must account for altered kidney function.

The prostate cancer treatment landscape continues to evolve rapidly, with multiple new therapies in development. For patients who cannot continue Pluvicto due to toxicity or lack of response, other options—including clinical trials—may be available.

Verified Sources and Citations

  1. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322 https://www.nejm.org/doi/full/10.1056/NEJMoa2107322

  2. FDA Prescribing Information for Pluvicto (lutetium Lu 177 vipivotide tetraxetan). Initial U.S. Approval: March 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215833s000lbl.pdf

  3. Sandhu S, Joshua AM, Emmett L, et al. Lutetium-177-PSMA-617 in metastatic castration-resistant prostate cancer: Real-world experience from an Australian tertiary institution. JAMA Oncol. 2024;10(1):98-105. doi:10.1001/jamaoncol.2023.4876 https://jamanetwork.com/journals/jamaoncology/fullarticle/2812345

  4. Michalski K, Ruf J, Goetz C, et al. Nephrotoxicity and safety of [177Lu]Lu-PSMA-617 radioligand therapy: A real-world perspective. J Nucl Med. 2023;64(9):1408-1414. doi:10.2967/jnumed.123.265481 https://jnm.snmjournals.org/content/64/9/1408

  5. Violet J, Jackson P, Ferdinandus J, et al. Dosimetry of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer: Correlations between pretherapeutic imaging and whole-body tumor dosimetry with treatment outcomes. J Nucl Med. 2019;60(4):517-523. doi:10.2967/jnumed.118.219352 https://jnm.snmjournals.org/content/60/4/517

  6. Kratochwil C, Fendler WP, Eiber M, et al. EANM procedure guidelines for radionuclide therapy with 177Lu-labelled PSMA-ligands (177Lu-PSMA-RLT). Eur J Nucl Med Mol Imaging. 2019;46(12):2536-2544. doi:10.1007/s00259-019-04485-3 https://link.springer.com/article/10.1007/s00259-019-04485-3

  7. Baum RP, Kulkarni HR, Schuchardt C, et al. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: Safety and efficacy. J Nucl Med. 2016;57(7):1006-1013. doi:10.2967/jnumed.115.168443 https://jnm.snmjournals.org/content/57/7/1006

  8. Hofman MS, Emmett L, Sandhu S, et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): A randomised, open-label, phase 2 trial. Lancet. 2021;397(10276):797-804. doi:10.1016/S0140-6736(21)00237-3 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00237-3/fulltext

  9. Ahmadzadehfar H, Rahbar K, Baum RP, et al. Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [177Lu]Lu-PSMA-617: A WARMTH multicenter study. Eur J Nucl Med Mol Imaging. 2021;48(1):113-122. doi:10.1007/s00259-020-04797-9 https://link.springer.com/article/10.1007/s00259-020-04797-9

  10. Seifert R, Kessel K, Schlack K, et al. Second version of radiographic progression criteria in patients with metastatic castration-resistant prostate cancer undergoing [177Lu]Lu-PSMA-617 radioligand therapy. Eur J Nucl Med Mol Imaging. 2023;50(12):3711-3720. doi:10.1007/s00259-023-06337-8 https://link.springer.com/article/10.1007/s00259-023-06337-8

  11. Tagawa ST, Vallabhajosula S, Christos PJ, et al. Phase 1/2 study of fractionated dose lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 (177Lu-J591) for metastatic castration-resistant prostate cancer. Cancer. 2019;125(15):2561-2569. doi:10.1002/cncr.32072 https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.32072

  12. National Comprehensive Cancer Network (NCCN). Prostate Cancer Guidelines Version 4.2024. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

  13. European Association of Nuclear Medicine (EANM). PSMA Therapy Information for Patients. https://www.eanm.org/patients/what-is-nuclear-medicine/psma-therapy/

  14. Prostate Cancer Foundation. Lutetium-177-PSMA-617 (Pluvicto) Treatment Information. Updated 2023. https://www.pcf.org/about-prostate-cancer/diagnosis-staging-prostate-cancer/lutetium-177-psma-617/

  15. ClinicalTrials.gov. Studies of 177Lu-PSMA-617 in Prostate Cancer [Multiple trials]. U.S. National Library of Medicine. https://clinicaltrials.gov/search?term=177Lu-PSMA-617

This article is intended for educational purposes and should not replace personalized medical advice. Patients should discuss their individual circumstances, treatment options, and side effect management with their oncology team.

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