Kidney numbers, and what FLOW showed

The three numbers, in plain words

Kidney results look intimidating and are actually fairly simple once the words are unpacked.

Creatinine is a waste product your muscles produce at a steady rate. Healthy kidneys clear it, so a rising creatinine usually means less is being cleared. It is measured directly.

eGFR — estimated glomerular filtration rate — is not measured at all. It is calculated from your creatinine along with your age and sex, and it estimates how much fluid your kidneys filter per minute. Because it is an estimate built from creatinine, anything that changes your creatinine for non-kidney reasons changes your eGFR too. Large muscle mass pushes creatinine up and eGFR down without any kidney problem existing; the reverse happens with very low muscle mass.

uACR — urinary albumin-to-creatinine ratio — is a urine test looking for albumin, a protein that healthy kidneys mostly keep hold of. Albumin leaking into urine is often the earliest sign of kidney damage, frequently appearing years before eGFR moves. It is arguably the more informative of the two and it is the one most often missing from a results letter.

Together they are how kidney disease gets staged. Neither alone tells the story.

What FLOW was and what it found

FLOW (Perkovic, New England Journal of Medicine, 2024) enrolled 3,533 people who had both type 2 diabetes and chronic kidney disease, defined by their eGFR and albumin levels — so a group already living with meaningful kidney impairment, not people with normal kidneys. They received semaglutide 1.0 mg weekly or placebo, on top of standard care, which for most participants included a renin-angiotensin system blocker.

The primary endpoint was a composite of kidney failure, a substantial sustained fall in eGFR, or death from kidney or cardiovascular causes. Semaglutide reduced that composite, with a hazard ratio of 0.76 and a 95 per cent confidence interval of 0.66 to 0.88 — around a 24 per cent relative reduction.

The trial was stopped early, at a pre-specified interim analysis, because the benefit had been demonstrated. That is a meaningful signal in itself and it is also a known source of effect-size inflation, which is the sort of thing our reading group is careful to flag in both directions. Cardiovascular and all-cause mortality also favoured semaglutide.

This landed as a genuinely significant result, because options that slow kidney disease progression are few, and because it extended what these drugs are for well beyond glucose and weight.

The limits of that finding

Everyone in FLOW had type 2 diabetes. Everyone in FLOW had chronic kidney disease at enrolment. That is who the answer is about.

It does not establish that these medicines protect the kidneys of people with normal kidney function. It does not establish anything about people with kidney disease who do not have diabetes. It tested semaglutide at 1.0 mg — the diabetes dose — not the higher weight-management dose, and not tirzepatide, and not liraglutide.

Sunil’s recurring complaint applies here as much as anywhere. Within about a fortnight of publication, we were seeing "these drugs protect your kidneys" stated flatly, with no population attached. What FLOW showed is that in people with type 2 diabetes and established kidney disease, on top of standard care, semaglutide 1.0 mg slowed progression. That is a substantial and specific finding, and it is not the general claim.

The kidney risk that actually turns up in this community

Mira wants this section read twice, because it is the one that affects people here week to week — and it has nothing to do with the trial.

The realistic kidney risk on these medicines is acute kidney injury from dehydration. A bad run of vomiting or diarrhoea, especially after a dose increase, especially in hot weather, especially in someone also taking a diuretic, an ACE inhibitor or an ARB, and sometimes with anti-inflammatories on top — that combination can drop kidney function fast. It is well recognised in the safety reporting for this whole drug class and it is the mechanism behind most kidney-related admissions members here have described.

The practical implication is unglamorous and effective. If you cannot keep fluids down for more than about a day, that is a call to a clinician, not something to ride out. Many people with type 2 diabetes have been given sick-day guidance about which medicines to pause temporarily during vomiting or diarrhoea — if you take any of those, ask whether such guidance applies to you, and get it in writing before you need it rather than during.

Hydration and electrolytes and nausea, honestly cover keeping fluids in. When a symptom needs a clinician covers the threshold.

Reading your own kidney results

A few things members find steadying.

• eGFR wobbles. Small movements between tests are extremely common and are frequently hydration, timing, or the calculation rather than your kidneys. A trend over a year is the thing to look at.
• An early dip is not always bad news. Several treatments that protect kidneys long term cause a small initial fall in eGFR as pressure inside the filtering units changes. Whether and how that applies to you is a question for the person following your kidney function — it is a well-described pattern, not a reason to self-interpret.
• Ask whether a uACR was done. It frequently is not, and it is often the more useful number. It is a urine sample, not a blood test.
• Muscle matters for the maths. If you have been lifting seriously, or if you have lost a lot of muscle, say so — it changes how creatinine-based estimates should be read. Keeping your strength is relevant for other reasons too.
• Bring the previous result. The whole guide at reading your bloodwork is built on this principle.

If you have kidney disease and are considering this

Members in our bloodwork-buddies circle with existing kidney disease consistently report two things. The first is that FLOW made the conversation with their diabetes or renal team markedly easier, because there is now a trial to point at. The second is that dose and monitoring genuinely differ for them, and that copying what someone without kidney disease is doing would be a mistake.

Questions that have worked: does the FLOW population look like me? Would this be at the diabetes dose or higher, and why? How often will my kidney function be checked once we start or change something? What are my sick-day instructions if I cannot keep fluids down?

Maryam wrote that the last of those was the most useful sentence she took into an appointment in three years — not because the answer was complicated, but because nobody had ever offered it and she had assumed she was supposed to already know.