New rat studies add kidney and vision protection to HNG evidence

One study induced diabetic kidney disease in mice and then treated them with HNG ¹. A second study temporarily blocked blood flow to rat kidneys and gave HNG before blood flow returned ². The third study used rats born with a form of inherited retinal degeneration and measured whether HNG changed gene activity and vision ³. None of these were human trials, so the results tell us about early clues, not clinical care.

The diabetic mouse study found an effect that grew with the amount of HNG given ¹. Mice given the highest amount of HNG had a 49.5% drop in the albumin-to-creatinine ratio, a urine marker used to track kidney damage ¹. The same mice showed less structural injury in kidney tissue than untreated diabetic mice. The researchers then looked at how HNG might be working. Tubular cell death by necroptosis, a type of cell suicide that can trigger inflammation, fell by 52.2% based on a key protein marker ¹. HNG also reduced mitochondrial damage and kept DNA from leaking out of mitochondria, which stopped a protein called ZBP1 from switching on this death pathway. The results were repeated in a second diabetic mouse strain and in human kidney tubule cells exposed to high sugar and fat ¹. The study also confirmed that kidney samples from people with diabetic nephropathy had more of this death pathway active, but it did not test HNG in those people ¹.

A separate rat study used a different injury: a blocked kidney artery followed by restored blood flow, known as ischemia-reperfusion injury ². HNG did not change two classic kidney function blood tests, blood urea nitrogen and serum creatinine, which were raised by the injury ². What it did change were markers of oxidative stress and inflammation inside the kidney tissue. Glutathione, an antioxidant, and superoxide dismutase, an enzyme that clears harmful oxygen molecules, recovered more in HNG-treated rats ². A tissue-inflammation marker and a lipid-damage marker both fell, and the kidney cells showed more ATP, the molecule cells use for energy ². Fewer kidney cells were dying by apoptosis, a distinct form of cell death ². The researchers also saw more activity in two protective signaling pathways called STAT3 and ERK1/2 ². This result is useful but limited because the standard blood tests did not improve within the short 24-hour follow-up.

The third study tested HNG in Royal College of Surgeons rats, a strain that loses retinal cells because of a genetic defect in the retinal pigment epithelium ³. The rats received either a lower or a higher HNG dose twice a week for up to four weeks ³. The most notable finding was in visual acuity, measured by optokinetic testing, which tracks how well a rat follows moving stripes. Rats given the higher dose showed significant improvement in visual acuity after four weeks, while the lower dose did not show that gain ³. On electroretinography, a direct measure of the retina's electrical response to light, neither dose changed the result compared with saline ³. Gene analysis found that the higher dose changed many genes involved in cell death, oxidative stress, inflammation, and retina function ³. The study suggests HNG may support vision through gene-level changes even when the standard electrical test stays flat, though the study does not explain exactly how that happens.

Before these three studies, HNG had already shown protective effects in cells and animals across several organs ⁴. In the kidney, a 2023 rat study reported that a humanin analogue improved diabetic nephropathy ⁴. The new mouse study adds a specific mechanism, showing that HNG blocks a mitochondrial DNA leak that can feed necroptosis ¹. In the eye, earlier cell studies found that HNG protected retinal pigment epithelial cells from oxidative stress and reduced markers tied to abnormal blood vessel growth in age-related macular degeneration ⁵. The new rat study is different because it used a live animal with inherited degeneration and measured vision, not just cell survival ³. Across the three new animal studies, the results are not identical. Diabetic kidney damage improved on one urine marker, short-term blood-flow kidney injury did not improve on standard blood tests, and high-dose HNG improved visual acuity without changing electroretinography ¹.

The biggest gap is human evidence. All three studies ran in animals or cells, and the kidney results were not uniform. In the short-term kidney blood-flow model, standard kidney function tests did not improve, so any protection may not show up on the blood tests doctors typically track ². The diabetic kidney study used urine and tissue markers, not survival or long-term kidney function, and it stopped short of testing HNG in people ¹. The eye study lasted only four weeks, so it cannot say whether vision gains persist or whether a different dose or timing would work better ³. The data also do not show whether HNG has the same effects in human kidneys or eyes, or whether it has any safety issues that would appear only in longer studies. In the research so far, HNG continues to show tissue protection in animal models, but the mixed kidney result and the short eye follow-up leave the practical value open.