- Design
- Individual-patient meta-analysis of 49 randomised trials
- Population
- 66,449 participants in CKD progression trials
- Primary outcome
- Association between early GFR change and albuminuria change, across trials and within patients
- Effect
- Trial-level slope 0.00 (−0.08 to 0.09); per SD GFR decline, ACR −8.0% (treatment) vs −6.6% (control)
This individual-patient meta-analysis used data from 49 randomised trials of CKD progression with 66,449 participants. It looked at early GFR change from baseline to three months and albuminuria change to six months, both across trials and within individuals.
Across trials, there was no relationship between a treatment's average early effect on GFR and its effect on albuminuria (slope 0.00). Within individuals, a greater early GFR decline went with a fall in albumin-creatinine ratio — 8.0% per standard deviation in treatment arms and 6.6% in control arms. The association was seen across drug classes except immunosuppression.
The common bedside reasoning is that a patient whose eGFR dips and albuminuria falls after starting a drug is a 'responder'. Because the same pattern appeared in patients on placebo, these early changes may mostly reflect natural variation and the course of the disease. The practical lesson is not to judge an individual's response, or decide to stop a proven drug, on early changes alone. Albuminuria remains a valid marker of risk and a trial-level surrogate; the caution is about reading it for one patient over a few months.
- Do not label an individual patient a responder or non-responder on early eGFR or albuminuria changes alone.
- Continue proven kidney-protective therapy even if albuminuria does not fall in the first months.
- Repeat albumin-creatinine ratio measurements; single values vary considerably.
- Use albuminuria to assess risk and guide intensity of overall management, not as proof of one drug's effect.
- The association was not seen in immunosuppression trials, so this caution applies mainly to other drug classes.
Why it matters
It challenges the habit of judging drug response in one patient from early albuminuria and eGFR shifts.
Don't overread it
This does not undermine albuminuria as a risk marker or as a surrogate at the level of trials.
The statistics, in plain English
A meta-regression slope of 0.00 (credible interval −0.08 to 0.09) means trials that lowered GFR more early on did not lower albuminuria more. Within patients, the GFR–albuminuria link was almost as strong on placebo (6.6%) as on treatment (8.0%), which points to factors other than the drug.
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