A new study in mice provides insights into why females in their reproductive years appear to be relatively protected from chronic kidney disease, a leading public health concern. The study reports that estrogen-regulated signaling promotes the regeneration of key filtration cells in female kidneys. The study also links pregnancy complications like preeclampsia to failures in this regenerative process. Chronic kidney disease (CKD) – which affects more than 10% of the global population – is a leading public health concern, not only because it can lead to fatal kidney failure, but also because it increases the risk of cardiovascular disease. Within the next 20 years, CKD is expected to become the fifth leading cause of death globally. Previous research has shown that sex differences play a notable role in disease progression: men are at higher risk for CKD, while women of reproductive age appear to be relatively protected. Although this suggests that female sex hormones, like progesterone and estrogen, may have a protective effect in the development of CKD, the mechanisms underlying the observed sex-based differences in disease susceptibility remain poorly understood.

Through lineage tracing, single-cell RNA sequencing, and an analysis of mouse models and human tissue and urine samples, Carolina Conte and colleagues show that female kidneys possess a greater capacity to regenerate key filtering cells, called podocytes, from renal progenitor cells. The cells are regenerated through estrogen receptor–dependent signaling, which protects against kidney disease and hypertension during reproductive years. What’s more, the authors found that this effect intensified in pregnant mice as kidneys adapted to a higher workload. However, when this regenerative capability is compromised, such as in preeclampsia, mouse mothers face heightened long-term risks of kidney disease and hypertension. At the same time, their offspring are predisposed to poor nephron development, low birth weight, and later-life cardiovascular and renal problems. According to Conte et al., the findings indicate that preeclampsia may arise from a failure of kidney progenitor cells to supply sufficient podocytes, linking maternal kidney health directly to pregnancy outcomes. This link offers new insights into potential therapeutic opportunities.

For reporters interested in topics related to research integrity, study co-author Paola Romagnani commented, “in nephrology and biomedical research, recent efforts have emphasized transparency through data sharing, standardized protocols, and independent replication. I believe future progress should focus on wider adoption of open-access datasets and stronger international collaborations, which are essential to ensure reproducibility and maintain trust in scientific findings.”

Following injury from a heart attack, immune cells called neutrophils release a peptide that punctures stressed heart cells and destabilizes their electrical activity. This triggers life-threatening arrhythmias. These findings offer a novel explanation – and potential therapeutic target – for these deadly cardiac events. Ischemic heart disease – cardiac damage caused by narrowed coronary arteries – is among the leading causes of death worldwide. It can lead to heart attacks and sudden cardiac death. When a coronary artery becomes blocked, cardiomyocytes experience oxygen deprivation, which disrupts their ability to manage ions like sodium and calcium, leading to dangerous electrical instability and life-threatening arrhythmias, for which there are few treatment options beyond defibrillation. Most arrhythmias occur within the first 2 days after a heart attack, which coincides with the characteristic cellular inflammatory response to the cardiac injury. Neutrophils, which are recruited in high numbers during this response, are known to interfere with normal cellular electrical conduction and are implicated in unintended tissue damage. While this highlights neutrophils as a potential target for future therapies, their full role in promoting arrhythmias isn’t fully understood.

Using mouse models of ischemic injury alongside human tissue and cell studies, Nina Kumowski and colleagues identified the peptide resistin-like molecule γ (Retnlg or RELMγ) as a key neutrophil-derived factor that promotes arrhythmias after a heart attack. According to Kumowski et al., RELMy – an antimicrobial pore-forming peptide – destabilizes heart rhythm by binding to and attacking stressed cardiomyocytes. Once bound, the peptide punctures the cardiomyocyte membranes, creating pores that alter cellular ion flux, triggering delayed depolarization, cell death, and the formation of tissue abnormalities that promote arrhythmia. In mouse models, removing RELMγ from neutrophils reduced ventricular arrhythmia 12-fold, supporting findings that the peptide drives electrical instability in the injured heart. Notably, the human homolog of this peptide, resistin (RETN), was detected in infarcted human myocardial tissue samples, and higher circulating RETN levels correlated with worse patient outcomes, highlighting its potential clinical relevance. In a related Perspective, Edward Thorp discusses the study in greater detail.