ArticleFrontiers in pharmacology2013
PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy.
Article in Frontiers in pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Pooled it
- Clinical safety, tolerability, pharmacokinetics and effects on urinary electrolyte excretion of AZD9977, a novel, selective mineralocorticoid receptor modulator.British journal of clinical pharmacology · 2018Trial
- Sex differences in the renal T cell profile in DOCA-salt hypertension are independent of MR activation and increases in blood pressure.American journal of physiology. Renal physiology · 2026Article
- Recent advances in mineralocorticoid receptor antagonists for heart failure with preserved ejection fraction: focus on finerenone in the era of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists.Frontiers in pharmacology · 2025Review
- Clinical implications of mineralocorticoid receptor overactivation.Clinical kidney journal · 2025Review
- Aldosterone and Potassium in Heart Failure: Overcoming This Major Impediment in Clinical Practice.Cardiac failure review · 2024Review
- Mineralocorticoid receptor antagonist use in chronic kidney disease with type 2 diabetes: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA).Clinical kidney journal · 2023Article
- Steroidal or non-steroidal MRAs: should we still enable RAASi use through K binders?Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- The Nonsteroidal Mineralocorticoid-Receptor-Antagonist Finerenone in Cardiorenal Medicine: A State-of-the-Art Review of the Literature.American journal of hypertension · 2023Review
- Biglycan Is a Novel Mineralocorticoid Receptor Target Involved in Aldosterone/Salt-Induced Glomerular Injury.International journal of molecular sciences · 2022Article
- Finerenone: A Potential Treatment for Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus.TouchREVIEWS in endocrinology · 2021Review
- Mineralocorticoid Receptor Antagonism in Chronic Kidney Disease.Kidney international reports · 2021Review
- Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp14 RNA cap methyltransferase.The Biochemical journal · 2021Article
- Author's overview: identifying SARS-CoV-2 antiviral compounds.The Biochemical journal · 2021Review
- Chronic Kidney Disease as a Systemic Inflammatory Syndrome: Update on Mechanisms Involved and Potential Treatment.Life (Basel, Switzerland) · 2021Review
- Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine.European heart journal · 2021Review
- The Non-Steroidal Mineralocorticoid Receptor Antagonist KBP-5074 Limits Albuminuria and has Improved Therapeutic Index Compared With Eplerenone in a Rat Model With Mineralocorticoid-Induced Renal Injury.Frontiers in pharmacology · 2021Article
- Mineralocorticoid Receptor Blockers: Novel Selective Nonsteroidal Mineralocorticoid Receptor Antagonists.Current hypertension reports · 2020Review
- Hyperkalemia: pathophysiology, risk factors and consequences.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019Review
- Mineralocorticoid Antagonism and Diabetic Kidney Disease.Current diabetes reports · 2019Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mineralocorticoid receptor (MR) antagonists PF-03882845 and eplerenone were evaluated for renal protection against aldosterone-mediated renal disease in uninephrectomized Sprague-Dawley (SD) rats maintained on a high salt diet and receiving aldosterone by osmotic mini-pump for 27 days. Serum K(+) and the urinary albumin to creatinine ratio (UACR) were assessed following 14 and 27 days of treatment. Aldosterone induced renal fibrosis as evidenced by increases in UACR, collagen IV staining in kidney cortex, and expression of pro-fibrotic genes relative to sham-operated controls not receiving aldosterone. While both PF-03882845 and eplerenone elevated serum K(+) levels with similar potencies, PF-03882845 was more potent than eplerenone in suppressing the rise in UACR. PF-03882845 prevented the increase in collagen IV staining at 5, 15 and 50 mg/kg BID while eplerenone was effective only at the highest dose tested (450 mg/kg BID). All doses of PF-03882845 suppressed aldosterone-induced increases in collagen IV, transforming growth factor-β 1 (Tgf-β 1), interleukin-6 (Il-6), intermolecular adhesion molecule-1 (Icam-1) and osteopontin gene expression in kidney while eplerenone was only effective at the highest dose. The therapeutic index (TI), calculated as the ratio of the EC50 for increasing serum K(+) to the EC50 for UACR lowering, was 83.8 for PF-03882845 and 1.47 for eplerenone. Thus, the TI of PF-03882845 against hyperkalemia was 57-fold superior to that of eplerenone indicating that PF-03882845 may present significantly less risk for hyperkalemia compared to eplerenone.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.