- Design
- double-blind, randomised, placebo-controlled trial over six months
- Population
- 72 patients with chronic kidney disease stage 3 or 4
- Primary outcome
- change in estimated glomerular filtration rate
- Effect
- eGFR reported to rise significantly with probiotic and fall significantly with placebo, magnitudes not given in the abstract; no progression in the probiotic group vs 8.6% with placebo; urinary indoxyl sulfate unchanged
The gut-kidney axis has been a plausible target in chronic kidney disease for years, on the theory that reducing bacterial production of uraemic toxins such as indoxyl sulfate slows progression. This double-blind, placebo-controlled trial randomised 72 patients with CKD stage 3 or 4 to Lactobacillus plantarum at 10^10 colony-forming units daily or placebo for six months, with change in eGFR as the primary outcome.
The reported result is favourable. eGFR rose significantly in the probiotic group and fell significantly on placebo, treatment assignment was the only independent predictor of eGFR change, and the effect was seen across stages 3 and 4 and in both diabetic and non-diabetic patients. No patient on probiotic progressed, against 8.6% on placebo.
The mechanism did not behave. Urinary indoxyl sulfate did not differ between groups, and its change did not correlate with eGFR improvement, so whatever produced the result was not the pathway the trial was built on. The authors say as much.
Two things should hold a reader back. The first is size: 72 patients over six months, with progression events in the single figures, is far too small to establish an effect on kidney function, and an eGFR that rises over six months in stage 3-4 disease is unusual enough to want confirming. The second is the reporting. The abstract states that eGFR changed significantly in both directions without giving the magnitude of either change or a confidence interval, which makes the result impossible to judge. A rise of 1 mL/min/1.73 m2 and a rise of 8 would mean entirely different things, and until the full paper supplies them this cannot be acted on. Probiotics are inexpensive and widely taken in India already; that is a reason for a proper trial, not a reason to recommend them.
- Do not recommend probiotics to slow CKD progression on this evidence
- Note that the proposed mechanism failed: urinary indoxyl sulfate did not differ between groups
- Ask for the magnitude of an eGFR change, not just its significance, before acting on any progression trial
- Keep the interventions with established effect in view: blood pressure control, RAS blockade, SGLT2 inhibition and glycaemic control
- Treat a six-month eGFR change as a short-term signal; CKD progression trials are normally judged over years
The statistics, in plain English
Statistical significance without an effect size is uninterpretable: it says a difference is unlikely to be chance, not that it is large enough to matter, and with 72 patients even a modest imbalance at baseline can produce one. The progression comparison, zero against 8.6%, rests on roughly three events, which is too few to support any estimate. The failure of indoxyl sulfate to move is the most informative negative here, because it removes the prespecified mechanism and leaves the finding without an explanation; results that work through no identifiable pathway are the ones that most often fail to replicate.
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