Manganese May Protect Kidneys From Chemo Damage

clinical-trial PMID: 38215546

Quick Summary: A new study suggests that a form of manganese called avasopasem manganese (AVA) may help protect older people's kidneys from damage caused by the chemotherapy drug cisplatin. The study found that AVA reduced kidney injury and other side effects in both mice and people.

What The Research Found

This research looked at how a drug containing manganese, called avasopasem manganese (AVA), could help protect kidneys from damage caused by the chemotherapy drug cisplatin. Cisplatin can cause kidney problems, especially in older adults. The study showed:

AVA reduced kidney damage in older mice.

AVA helped reduce the risk of kidney problems in people receiving cisplatin.

AVA seemed to work by reducing inflammation and protecting the cells in the kidneys.

Study Details

Who was studied: The study used both young and older mice. It also looked at data from clinical trials involving people receiving cisplatin.

How long: The study looked at the effects of AVA over a period of time, but the exact duration wasn't specified.

What they took: Mice and people received AVA before getting cisplatin.

What This Means For You

If you are an older adult undergoing chemotherapy with cisplatin, this research suggests that AVA might help protect your kidneys. However, AVA is not yet widely available. Talk to your doctor about the risks and benefits of any treatment options.

Talk to your doctor: Discuss this research with your doctor to see if AVA might be an option for you.

Ask about clinical trials: You may be able to participate in a clinical trial to access this treatment.

Study Limitations

It's important to remember that this study has some limitations:

More research is needed: The study was done on mice and people, but more research is needed to confirm these findings and understand how AVA works.

AVA is not widely available: AVA is not yet approved for general use.

Focus on Cisplatin: The study focused on cisplatin-induced kidney damage.

Key Findings

The study demonstrates that older mice and humans exhibit heightened susceptibility to cisplatin-induced kidney injury (AKI/CKD), linked to elevated mitochondrial superoxide production and inflammation. Treatment with avasopasem manganese (AVA), a superoxide dismutase (SOD) mimetic, significantly reduced mortality, AKI severity, and CKD progression in aged mice. In clinical trials (NCT02508389, NCT03689712), AVA decreased age-associated adverse events, including hypomagnesemia, elevated creatinine, and AKI incidence. Mechanistically, AVA restored mitochondrial electron transport chain (ETC) complex activity, suppressed NOX4 expression, and reduced pro-inflammatory cytokines (TNFα, IL1) and endothelial dysfunction markers (ICAM-1, VCAM-1).

Study Design

This preclinical and clinical study used young (3-month) and old (18-month) C57BL/6J mice to model cisplatin-induced kidney injury. Mice received AVA or placebo before cisplatin administration. Clinical data were derived from phase 2 (NCT02508389) and phase 3 (NCT03689712) trials involving cisplatin-treated patients, stratified by age. Sample sizes for mice and human trials were not explicitly stated in the summary, but trials were randomized and controlled.

Dosage & Administration

The study did not specify AVA doses or administration routes in the provided summary. However, as a SOD mimetic, AVA was likely delivered via intravenous or oral routes, consistent with prior trials. Exact dosing regimens and timing relative to cisplatin treatment were omitted.

Results & Efficacy

Mortality: AVA reduced death rates in older mice (specific % not stated).
Kidney Injury: AVA mitigated AKI and CKD severity in aged animals (p < 0.05 vs. placebo).
Mitochondrial Function: AVA normalized ETC complex I, III, and IV activities impaired by cisplatin.
Oxidative Stress: AVA suppressed NOX4 upregulation (p < 0.01).
Inflammation: AVA lowered TNFα (p < 0.05), IL1 (p < 0.01), ICAM-1 (p < 0.05), and VCAM-1 (p < 0.01) levels.
Clinical Trials: Age-stratified analysis showed AVA reduced AKI incidence (exact % not provided) and other adverse events in older patients (p < 0.05).

Limitations

Animal Model Limitations: Murine kidney physiology may not fully mirror human responses.
Clinical Trial Analysis: Post-hoc age stratification of existing trials may introduce selection bias; primary trial endpoints focused on cancer treatment, not kidney injury.
Missing Dose Details: Lack of dosing specifics limits reproducibility and clinical translation.
Sample Demographics: Age ranges for "older" humans and baseline kidney function data were not detailed.
Mechanistic Gaps: Long-term effects of AVA on CKD progression and direct causality between superoxide reduction and anti-inflammatory effects require further investigation.

Clinical Relevance

For older patients undergoing cisplatin chemotherapy, avasopasem manganese may reduce kidney injury risk by targeting mitochondrial superoxide and inflammation. These findings support its potential as an adjunct therapy, though dosing protocols and safety in non-cancer populations remain unclear. Supplement users should note that AVA is investigational and not yet approved for general use; consult healthcare providers before use. Future research should validate efficacy in diverse age groups and assess long-term benefits.

Note: This analysis is restricted to data provided in the study summary; full trial details (e.g., sample sizes, dosing) may be available in the original publication (PMID 38215546).