Protein in Urine

What Makes the Kidney's Filter Start Leaking

The evidence here is strong for the mechanism and growing for what to do about it. Protein in the urine means the kidney's filter is letting through molecules it should hold back. Normally almost no protein escapes. When it does, that signals damage to the filtering units, and it predicts how fast kidney function will decline. Gut bacteria produce at least one compound that causes this directly.

The cells that do the filtering

The filter has three layers, and the outermost is the interesting one.

Podocytes are specialised cells that wrap around the tiny blood vessels of each filtering unit. They extend interlocking foot-like projections, leaving narrow slits between them.

Those slits set the size limit. Water and small waste molecules pass. Proteins like albumin are held back.

When podocytes are damaged, the projections flatten out and the slits widen. Protein escapes into the urine. Podocytes also barely regenerate, so damage tends to be permanent.

A bacterial compound that damages them

Researchers looking for what injures podocytes in diabetes found a compound made in the gut.

Gut bacteria convert tyrosine, an amino acid from protein in food, into phenol. The liver then attaches a sulfate group, producing phenyl sulfate.

Given to animals with diabetes, phenyl sulfate on its own induced protein leakage into the urine and visible podocyte damage under the microscope.

The human data followed the same line. In a cohort of people with diabetes, phenyl sulfate levels correlated with how much protein was already leaking, and with how much that leakage was predicted to worsen over the following two years.

Researchers then blocked the bacterial enzyme that makes phenol in the first place. Protein leakage in the diabetic animals fell.

That's a complete chain. A bacterial enzyme produces a compound, the compound damages the filter, and blocking the enzyme reduces the damage.

Source: Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease

Why the amino acid supply matters

The useful part of that chain is where it starts, because it starts with food.

Phenol comes from tyrosine reaching the large intestine undigested. The same fermentation of leftover protein produces indoxyl sulfate and p-cresyl sulfate, two other compounds that damage kidney tissue.

Gut bacteria ferment whatever arrives. Given fibre, they make short-chain fatty acids that nourish the gut lining. Given undigested protein and little fibre, they make these compounds instead.

So the balance of what reaches the large intestine shapes which set of products gets made.

What changing that balance has achieved

That prediction has been tested in people, and the results are consistent.

A review pooled 21 randomised trials covering 700 patients with kidney disease. Fibre supplementation, ranging from 6 to 50 grams a day for typically more than four weeks, significantly reduced p-cresyl sulfate, indoxyl sulfate and blood urea nitrogen. Inflammatory markers including interleukin-6 fell alongside.

A separate randomised trial gave 68 people with moderate kidney disease a resistant starch supplement for 16 weeks, resistant starch being a type of starch that escapes digestion and reaches the large intestine intact.

The effect sizes in the pooled analysis were modest rather than dramatic. What makes them worth taking seriously is the consistency, and that they moved the specific compounds the mechanism above implicates.

Source: Effects of High Amylose-Resistant Starch on Gut Microbiota and Uremic Toxin Levels in Patients With Stage-G3a-G4 Chronic Kidney Disease: A Randomized Trial

What this means for you

Protein or froth in the urine needs proper investigation, and blood pressure medication from the class that protects the kidney filter is the treatment with the strongest evidence behind it. In addition, the research above shows a compound made by gut bacteria causing protein leakage and podocyte damage on its own, with fibre lowering related compounds across 21 trials. A varied, plant-rich diet, adjusted with a renal dietitian if kidney function is already reduced, supports the same gut bacteria this research ties to fermenting fibre rather than leftover protein. That's the same idea behind GutLab, everyday gut health starts with regularly feeding the microbiome a broad range of plant-rich ingredients.