Heart and circulation
What does it do to the kidneys?
Kidney measures, which increasingly appear in the metabolic trials as a secondary result.
85,893
people in trials
22
human studies
8
compounds, animal or cell only
8
trials found nothing
Measured in people
Ranked by how many people, which is a fact about the evidence and not a judgement about the compound. The one at the top is the most studied, which is not the same as the best. Counts are never added across compounds, because the same person can appear in more than one trial.
- 53,026 people1 human study
UK Biobank proteomics, 53,026 participants, 13.3 years of follow-up: GDF15 was positively associated with 20 to 24 incident chronic diseases (hazard ratios 1.21 to 3.77) and with multimorbidity, with levels largely explained by renal function, liver function, inflammation and obesity.
Metabolism, 2025 · 53,026 people
- 8,410 people2 human studies1 found nothing
ASCEND-HF: 7,141 people hospitalised with acute heart failure randomised to nesiritide or placebo for 24 to 168 hours on top of standard care. Dyspnoea improvement 44.5 versus 42.1 percent at 6 hours and 68.2 versus 66.1 percent at 24 hours, neither meeting the prespecified threshold. Rehospitalisation or death within 30 days 9.4 versus 10.1 percent (difference -0.7 percentage points, 95 percent confidence interval -2.1 to 0.7). No excess worsening renal function; more hypotension. Funded by Scios, the manufacturer.
New England Journal of Medicine, 2011 · 7,141 people
found nothingMeta-analysis of 5 randomised studies, 1,269 patients. FDA-approved doses of nesiritide increased worsening renal function against non-inotrope control, relative risk 1.52, 95 percent confidence interval 1.16 to 2.00, p = 0.003. There was no difference in the need for dialysis. ASCEND-HF later found no excess renal harm in 7,141 people.
Circulation, 2005 · 1,269 people
- 7,637 people1 human study
DEVOTE: 7,637 people with type 2 diabetes, 85.2 percent with established cardiovascular or kidney disease, randomised double-blind to insulin degludec or glargine U100. Major cardiovascular events occurred in 8.5 versus 9.3 percent (hazard ratio 0.91, 95 percent confidence interval 0.78 to 1.06, non-inferior). Severe hypoglycaemia occurred in 4.9 versus 6.6 percent, an absolute difference of 1.7 percentage points (rate ratio 0.60, p < 0.001 for superiority). Sponsor Novo Nordisk.
New England Journal of Medicine, 2017 · 7,637 people
- 6,609 people1 human study
EMPA-KIDNEY. 6,609 people with chronic kidney disease, median 2.0 years. Kidney disease progression or cardiovascular death occurred in 13.1 percent against 16.9 percent (hazard ratio 0.72). Notably for anyone reading the drug as a mortality intervention, death from any cause was 4.5 percent against 5.1 percent and was not a significant difference in this trial.
New England Journal of Medicine, 2023 · 6,609 people
- 4,641 people2 human studies
TREAT: 4,038 people with type 2 diabetes, chronic kidney disease and anaemia randomised to darbepoetin alfa targeting 13 g/dL or to placebo with rescue below 9 g/dL. Death or a cardiovascular event, hazard ratio 1.05 (0.94 to 1.17); death or end-stage renal disease, hazard ratio 1.06 (0.95 to 1.19). Fatal or non-fatal stroke 101 versus 53, hazard ratio 1.92, 95 percent confidence interval 1.38 to 2.68, p < 0.001. Fewer transfusions (297 versus 496) and only a modest improvement in fatigue. Sponsor Amgen.
New England Journal of Medicine, 2009 · 4,038 people
CREATE: 603 people with estimated GFR 15 to 35 randomised to a normal (13.0 to 15.0 g/dL) or subnormal (10.5 to 11.5 g/dL) haemoglobin target using epoetin beta, 3 years. First cardiovascular events 58 versus 47, hazard ratio 0.78, 95 percent confidence interval 0.53 to 1.14, p = 0.20. More people in the normalisation group needed dialysis, 127 versus 111, p = 0.03. General health and physical function scores improved. Sponsor Hoffmann-La Roche.
New England Journal of Medicine, 2006 · 603 people
- 4,076 people1 human study
4,076 high-risk patients: MACE hazard ratio 0.73 and composite renal outcome hazard ratio 0.68 versus placebo.
New England Journal of Medicine, 2021 · 4,076 people
- 444 people1 human study
The only randomised human data on glutaminase inhibition. 444 patients with metastatic renal cell carcinoma. Median progression-free survival 9.2 months with telaglenastat plus cabozantinib versus 9.3 months with placebo plus cabozantinib, hazard ratio 0.94, P = 0.65. Manufacturer funded. Oncology, not senescence.
JAMA Oncology, 2022 · 444 people
Also measured, in animals or cells
Human cells and mice. GLS1 was identified as essential for the survival of human senescent cells: lysosomal damage lowers intracellular pH, inducing kidney-type glutaminase, whose ammonia production neutralises the acidity. Inhibiting it in aged mice eliminated senescent cells specifically and ameliorated age-associated organ dysfunction.
Science, 2021 · animal
- 409 people1 human study1 found nothing
found nothing409 patients: early vasopressin did not improve kidney-failure-free days, though renal replacement therapy use was lower.
JAMA, 2016 · 409 people
- 248 people1 human study
248 people with type 2 diabetes and chronic kidney disease (mean eGFR 55, 47 percent on SGLT2 inhibitors), 26 weeks, randomised to cotadutide 100, 300 or 600 mcg, placebo, or open-label semaglutide 1 mg weekly. Urine albumin to creatinine ratio fell 43.9 percent at 300 mcg (95 percent CI 30.6 to 54.7) and 49.9 percent at 600 mcg (38.4 to 59.3) against placebo at week 14, sustained to week 26. Serious adverse events balanced; tolerability at 600 mcg described as comparable to semaglutide. Sponsor funded (NCT04515849, results posted January 2025).
Kidney International, 2024 · 248 people
- 205 people1 human study1 found nothing
found nothing205 people with stage 3b or 4 chronic kidney disease randomised to nicotinamide 750 mg twice daily, lanthanum carbonate, both, or double placebo for 12 months. Neither drug significantly lowered serum phosphate or intact FGF23, the dual primary endpoints. Adverse event rates were similar across arms but gastrointestinal symptoms limited adherence. Another well-run, independently funded, multi-year nicotinamide trial that missed its primary endpoint.
Journal of the American Society of Nephrology, 2019 · 205 people
- 75 people1 human study
75 patients with acute heart failure given 0.0125 micrograms per kilogram per minute of carperitide for 6 hours. Lower baseline plasma ANP (r = -0.35, p = 0.002) and lower vasopressin (r = -0.54, p < 0.001) predicted a larger diuretic response; baseline blood pressure, renal function and prior loop diuretic use did not.
ESC Heart Failure, 2022 · 75 people
- 45 people1 human study1 found nothing
found nothingOpen-label, self-controlled trial, 45 subjects across healthy, cardiovascular-risk and dialysis groups, 4,000 FU/day for 2 months: fibrinogen fell 7 to 10%, factor VII 7 to 14%, factor VIII 17 to 19% (all p<0.001 for the time effect) across groups; no placebo or control arm, and blood lipids did not change.
Nutrition Research, 2009 · 45 people
- 42 people1 human study1 found nothing
found nothingNCT05038488. 42 adults hospitalised with COVID-19 and acute kidney injury randomised 3:2 to MIB-626 1.0 g or placebo tablets twice daily for 14 days. Blood NAD rose gradually from 16.0 to 25.5 to 42.6 micrograms per millilitre at baseline, day 5 and day 14, and NAD metabolites rose rapidly by day 3. Serum creatinine, cystatin C and serum markers of acute kidney injury did not differ between groups. Serum CRP, IL-6 and TNF alpha and indices of disease severity also did not differ. The authors attribute the absence of clinical effect to the slow rise in NAD and call for studies of parenteral administration. Two authors are employees of Metro International Biotech and a third is a consultant to the company.
FASEB BioAdvances, 2025 · 42 people
- 24 people1 human study1 found nothing
found nothingNCT03176628. 24 hospitalised patients with acute kidney injury received escalating doses of NRPT or placebo twice daily for 2 days across four dose steps up to 1000 mg NR with 200 mg pterostilbene. Acute kidney injury itself reduced whole blood NAD by 50 percent at 48 hours in placebo patients (P=0.05). Pooling all steps, NRPT increased NAD by 37 percent at 48 hours (P=0.002), but only one individual step reached significance and interindividual variability was considerable. Creatinine, eGFR, electrolytes, liver function tests and blood counts were unchanged. Three of 20 patients on NRPT reported minor gastrointestinal effects. Two authors are Elysium Health employees.
BMC Nephrology, 2020 · 24 people
- 2 people1 human study1 found nothing
found nothingTwo adults received 10 mg intravenously on day 1 and 20 mg on day 2. No adverse effects were reported and cardiac, liver, kidney, thyroid and glucose laboratory values did not change meaningfully. Two subjects cannot characterise safety.
Alternative Therapies in Health and Medicine, 2025 · 2 people
- no headcount stated1 human study
Human, and the largest body of TIMP-2 data in people, though it is not about ageing. Two multicentre observational studies in critically ill adults: 522 in discovery across sepsis, shock, major surgery and trauma cohorts with over 300 markers examined, and 728 in the Sapphire validation cohort. Urinary TIMP-2 combined with IGFBP7 gave an area under the curve of 0.80 for moderate to severe acute kidney injury within 12 hours, significantly better than all previously described markers (p < 0.002), none of which exceeded 0.72.
Critical Care, 2013 · no headcount in the line
- no headcount stated1 human study
A controlled clinical trial in humans. Significantly higher increases in muscle mass in participants dosed with ecdysterone, and significantly more pronounced increases in one-repetition bench press performance. The same hypertrophic effect appeared in C2C12 myotubes in vitro. No increase in liver or kidney toxicity biomarkers. Participants were screened for prohibited performance-enhancing substances and the supplement was tested for anabolic steroid contamination before administration. The authors conclude their results strongly suggest including ecdysterone on the prohibited list in class S1.2, other anabolic agents.
Archives of Toxicology, 2019 · no headcount in the line
- no headcount stated1 human study
A randomised controlled trial in dialysis patients, published in JAMA, reporting anabolic effects. One of the few randomised trials of an anabolic steroid in a major general medical journal, and the basis of the drug's renal indication.
JAMA, 1999 · no headcount in the line
- no headcount stated1 human study1 found nothing
found nothingSingle-centre open-label trial against dapagliflozin. 106 randomised, 80 completed. Urine albumin to creatinine ratio fell 29.3 percent on PEG-loxenatide against 31.8 percent on dapagliflozin over 24 weeks, a difference that was not significant. Glycated haemoglobin fell almost identically in both arms. Triglycerides fell more on PEG-loxenatide. Gastrointestinal adverse events were more common on PEG-loxenatide. Albuminuria is a surrogate marker; no kidney outcome such as dialysis, transplantation or doubling of creatinine was measured.
Frontiers in Endocrinology, 2024 · no headcount in the line
- no headcount stated1 human study
The safety report from the same 80-patient trial, 91.3 percent completion, average age 54, 71 percent female. No adverse drug reactions on hepatic, renal or glucose markers and no statistically significant self-reported or major adverse reactions. The stated conclusion is that pterostilbene is generally safe for use in humans up to 250 mg a day. It reports safety only and makes no efficacy claim.
Journal of Toxicology, 2013 · no headcount in the line
Measured in animals or cells, not yet in people
These are separated from the trials above rather than ranked against them, because they answer a different question. A result in a rat is a real result and a reason somebody ran the study; it is not a measurement of what happens in you. Where the human work is missing, the reason is usually money rather than failure, and that is set out at the bottom of this page.
- 1 preclinical study
Measured in animals or cells
A designed FOXO4 peptide that blocks the FOXO4-p53 interaction selectively triggered apoptosis in senescent cells and restored fitness, fur density and renal function in fast-aging XpdTTD/TTD and naturally aged mice.
Cell, 2017 · animal
- 1 preclinical study
Measured in animals or cells
Adipotide induced apoptosis in white-fat blood vessels of obese rhesus monkeys, producing 7.4 to 14.7% weight loss in four weeks with improved insulin resistance; renal proximal tubule changes were dose-dependent and reversible.
Science Translational Medicine, 2011 · animal
- 1 preclinical study
Measured in animals or cells
Mouse, physiologically ageing wild-type rather than progeroid. Long-term partial reprogramming regimens produced duration-dependent effects in kidney and skin, with reversion of epigenetic clock measures and reduced inflammation, senescence and stress-response gene expression. The authors make no lifespan extension claim for wild-type mice.
Nature Aging, 2022 · animal
- 1 preclinical study
Measured in animals or cells
Mouse, from the Yamada and Yamanaka laboratories. Transient expression of reprogramming factors followed by doxycycline withdrawal produced tumours in various tissues, consisting of undifferentiated dysplastic cells with global DNA methylation changes. Kidney tumours shared characteristics with Wilms tumour. Stem cells derived from those tumour cells gave rise to non-neoplastic kidney cells, proving the tumours were epigenetically rather than genetically driven.
Cell, 2014 · animal
- 1 preclinical study
Measured in animals or cells
Mouse ureteral obstruction model, with senescent tubular cells also observed in obstructed human kidney tissue. Procyanidin C1 reduced senescent tubular cells and renal fibrosis in the mice. The human component is tissue observation, not treatment.
FASEB Journal, 2025 · animal
- 1 preclinical study
Measured in animals or cells
The paper that put rilmenidine into geroscience. Identified by searching for compounds with a caloric-restriction-like expression signature. Increased lifespan in C. elegans when given at young and older ages, with the stress resilience, healthspan and lifespan benefits all dependent on the I1-imidazoline receptor nish-1, on DAF-16 and SKN-1, and on autophagy but not AMPK. Adding it to calorically restricted worms, reduced TORC1 function or rapamycin produced no further gain. Mice treated with rilmenidine showed caloric-restriction-like transcriptional changes in liver and kidney, which is a gene expression finding and not a lifespan finding. Two authors disclose commercial longevity interests.
Aging Cell, 2023 · animal
- 1 preclinical study
Measured in animals or cells
Synthesis and first characterisation. NMNH raised NAD to a much higher extent and faster than NMN or NR in mammalian cells, through an NRK-independent and NAMPT-independent pathway. It reduced damage and accelerated repair in renal tubular epithelial cells after hypoxia and reoxygenation injury. In mice, administration caused a rapid and sustained NAD surge in whole blood, with increases in liver, kidney, muscle, brain, brown adipose tissue and heart, but not in white adipose tissue.
FASEB Journal, 2021 · animal
- 1 preclinical study
Measured in animals or cells
Rats. Pretreatment with SS-20 thirty minutes before warm ischaemia raised tolerated ischaemia time from 30 to 45 minutes. It reduced cytoskeletal breakdown, cell swelling and mitochondrial matrix swelling, preserved cristae, improved state 3 respiration and respiratory control ratio in isolated kidney mitochondria, and reduced later interstitial fibrosis when given after ischaemia. A surgical-window result in rats, not a chronic kidney disease treatment in people.
American Journal of Physiology, Renal Physiology, 2015 · animal
Why the trial record looks like this
A missing trial is usually a missing sponsor. Nobody runs a nine-figure programme on a molecule they cannot own, so the compounds with the thinnest human records are often the oldest and most freely available ones rather than the weakest. Taking OSK Partial Reprogramming as the example, because it states the problem most clearly:
Partial reprogramming is the most heavily funded area in longevity biotechnology and the one with the least human data. Altos Labs launched in 2022 with about three billion dollars and has no registered human trial. YouthBio Therapeutics, Turn Biotechnologies and Retro Biosciences likewise return no genuine reprogramming trial on ClinicalTrials.gov. The single registered study in the world is Life Biosciences' ER-100, which this site also covers under its own entry. The gap between the money and the registry is the most informative fact on this page.
The reason for the gap is the safety problem, and it is not speculative. Two high-profile mouse papers, in Nature in 2013 and Cell in 2014, showed that transient induction of reprogramming factors in living animals produces teratomas across multiple organs and, when reprogramming is started and then stopped, tumours resembling paediatric Wilms tumour. The therapeutic window sits between not enough expression to rejuvenate and enough to dedifferentiate into cancer, it is defined by duration and dose, and it has only been characterised in mice. Dropping c-Myc to give OSK, and injecting into one eye with an oral switch that can be turned off, are both engineering responses to that problem. Neither has been shown to solve it in a person.
One further distinction is worth holding on to, because popular coverage collapses it constantly. The 2016 result that partial reprogramming extends lifespan is in a progeroid mouse, an animal engineered to age prematurely from a specific lesion. Reversing that lesion extends that animal's life without demonstrating anything about normal ageing. The one report of lifespan extension in normal mice is a 2024 paper in 124-week-old males from a single group, measuring remaining rather than total lifespan, and it has not been replicated.
A compound appears here only when a citation on its own page states this outcome and reports a result for it; naming it is not enough. Human, animal and cell work are counted separately and never merged. Participant counts are read from the study lines and deliberately undercount. Nothing here is advice, and nothing here is a recommendation to take or to avoid anything.