Kidney function: why you need two numbers, not one

Chronic kidney disease does not hurt. It does not cause fatigue or swelling until it is advanced, and by then much of the lost function cannot be recovered. Yet it can be detected years earlier with two inexpensive laboratory tests — one from blood, one from a urine sample. A large German analysis shows how often that chance is missed: of almost 450,000 people at risk who were treated in GP practices, only 28.6% had enough test results to diagnose or exclude kidney disease. Among those who met the criteria, 83.5% had no recorded diagnosis. (The InspeCKD analysis was funded by AstraZeneca, a manufacturer of kidney medication.)

Two pillars, not one

The first pillar is the estimated glomerular filtration rate (eGFR). It is calculated from the blood level of creatinine, a waste product of muscle, together with age and sex, and expresses how much blood the kidneys filter per minute (in ml/min per 1.73 m² of body surface). It measures how well the kidneys clear the blood.

The second pillar is the urine albumin-to-creatinine ratio (UACR), measured in a single spot urine sample. Albumin is a protein that healthy kidney filters hold back. When it leaks into the urine, the filters are damaged — often long before the eGFR falls. Albuminuria is also a strong marker of cardiovascular risk.

The international KDIGO guideline (2024) defines chronic kidney disease as abnormal kidney structure or function lasting at least three months — for example an eGFR below 60, or a UACR of 30 mg/g (3 mg/mmol) or more. It advises testing people at risk with both measurements.

The KDIGO heat map

KDIGO stages kidney disease on two axes at once:

• G categories (eGFR): G1 ≥90 · G2 60–89 · G3a 45–59 · G3b 30–44 · G4 15–29 · G5 <15 (kidney failure)
• A categories (UACR): A1 <30 mg/g (normal to mildly increased) · A2 30–300 mg/g (moderately increased) · A3 >300 mg/g (severely increased)

The resulting grid is coloured from green (low risk) through yellow and orange to red (very high risk). Risk climbs with each step along either axis. This is the point of the two-test approach: a normal eGFR with albuminuria is not a normal result. Someone at "G2 A2" has kidney disease, while someone at "G2 A1" without other signs of kidney damage does not.

Who should be tested

KDIGO names high blood pressure, diabetes and cardiovascular disease (including heart failure) as the main reasons to test. Other risk factors include older age, a family history of kidney disease, genetic risk, previous acute kidney injury, and regular use of drugs that can harm the kidneys, such as frequent painkillers. In diabetes, KDIGO advises annual testing, starting at diagnosis of type 2 diabetes and five years after the onset of type 1.

German guidance is less uniform. The National Disease Management Guideline (Nationale VersorgungsLeitlinie) for type 2 diabetes (2023) supports testing eGFR and UACR at least once a year. The guideline of the German College of General Practitioners and Family Physicians (DEGAM, 2019) recommends yearly eGFR in type 2 diabetes but UACR only for selected patients — for example those with poorly controlled blood sugar or blood pressure who are not yet on an ACE inhibitor or angiotensin receptor blocker. It advises against routine screening of adults without risk factors.

Why albuminuria is so often missed

Creatinine is part of almost every routine blood panel, so an eGFR appears automatically. The UACR has to be ordered deliberately, and a separate urine sample is needed. An earlier partial analysis of the German InspeCKD data found at least one creatinine test in 45.5% of at-risk patients but a UACR in only 0.4%. A single raised value is not enough, either: KDIGO advises confirming a UACR of 30 mg/g or more with repeat testing, because single values fluctuate.

Creatinine or cystatin C?

Because creatinine comes from muscle, the creatinine-based eGFR is least reliable at the extremes of body build. In frail older people with little muscle, it overestimates kidney function — which can lead to drugs being overdosed. Cystatin C, a protein produced by almost all cells, depends much less on muscle mass. KDIGO recommends a combined creatinine–cystatin C eGFR when the creatinine-based value is likely to be inaccurate (grade 1C), and using the combination whenever cystatin C is available (grade 1B).

The equations themselves have changed. Older US formulas included a correction for Black race; the CKD-EPI equations published in 2021 removed it, and KDIGO now advises that race should not be used to calculate eGFR.

Why it matters for medicines

Many common drugs are cleared by the kidneys. KDIGO advises considering kidney function whenever such drugs are dosed. For most people a creatinine-based eGFR is adequate, but for drugs with a narrow safety margin, or when creatinine is unreliable, the combined equation or a measured GFR may be needed. Knowing your eGFR is also useful before scans with contrast agents and before surgery.

Finding it early now changes outcomes

For decades, early kidney disease meant little more than controlling blood pressure. That has changed. In DAPA-CKD, 4,304 patients with an eGFR of 25–75 and a UACR of 200–5,000 mg/g received dapagliflozin or placebo. Over a median of 2.4 years, the combined endpoint of a major loss of kidney function, kidney failure, or death from kidney or cardiovascular causes occurred in 9.2% versus 14.5% (hazard ratio 0.61). Nineteen patients had to be treated to prevent one such event, and deaths fell from 6.8% to 4.7%. EMPA-KIDNEY enrolled 6,609 patients, including many with lower albuminuria, and found a similar benefit with empagliflozin: 13.1% versus 16.9% (hazard ratio 0.72), consistent in people with and without diabetes.

KDIGO 2024 now recommends these SGLT2 inhibitors for adults with CKD and an eGFR of at least 20 if the UACR is 200 mg/g or more, or if they have heart failure (grade 1A); they are suggested for an eGFR of 20–45 with lower albuminuria (grade 2B). For people with albuminuria, ACE inhibitors or angiotensin receptor blockers remain a cornerstone. Yet in the German InspeCKD data, only about one in ten patients with diagnosed CKD received both drug classes. Treatment cannot start if the disease is never found.

What this means for you

• If you have high blood pressure, diabetes, cardiovascular disease or a family history of kidney disease, ask for both an eGFR and a urine albumin-to-creatinine ratio — not just "kidney values".
• Ask for your result as a category, for example "G2 A1", and what colour it falls into on the KDIGO grid.
• An abnormal value should be repeated after about three months before it counts as chronic. KDIGO considers a fall in eGFR of more than 20% or a doubling of UACR between tests worth investigating.
• If you are very muscular, very slight, or frail, ask whether a cystatin C test would give a more reliable eGFR.
• Bring a full list of your medicines, including over-the-counter painkillers, to any appointment where kidney function is discussed.

For context on reading laboratory reports, see how to read your lab results; for diabetes testing, HbA1c versus fasting glucose.

This article is general information and not individual medical advice. Decisions about tests and treatment belong in a conversation with your own physician.