Insulin is technically small enough to pass through dialysis membranes, but in practice, it is not meaningfully removed into the dialysate fluid. At roughly 5,800 daltons, insulin falls within the molecular weight range that high-flux dialysis membranes can handle. Yet studies consistently find that insulin is undetectable in the dialysate or ultrafiltration fluids collected during hemodialysis sessions. The real story is more nuanced: insulin levels in the blood do drop during dialysis, but through a different mechanism than you might expect.
Why Insulin Doesn’t Cross Into the Dialysate
Dialysis membranes work by allowing molecules below a certain size to pass from the blood side to the dialysate side. Insulin’s molecular weight puts it right at the border of what standard low-flux membranes can filter, and well within the range for high-flux synthetic membranes. So in theory, some insulin should cross over.
In both laboratory and clinical studies, however, insulin is consistently absent from collected dialysate and ultrafiltration fluids. The reason is adsorption: insulin sticks to the membrane surface itself rather than passing through it. The dialyzer membrane acts more like a sponge for insulin than a filter. This adsorption effect varies by membrane material. Polysulfone membranes, one of the most commonly used synthetic materials, show significantly higher insulin clearance and reduction rates compared to cellulose triacetate membranes. But even with polysulfone, the insulin is being pulled out of the blood and trapped in the membrane, not washed into the waste fluid.
How Dialysis Still Affects Blood Insulin Levels
Even though insulin doesn’t technically dialyze in the traditional sense, plasma insulin levels do decline during a hemodialysis session. The membrane adsorption effect accounts for much of this. But the picture is complicated by the fact that the pancreas is simultaneously adjusting its own insulin output in response to changing blood sugar levels during the session.
The type of dialyzer matters. One study comparing high-flux and low-flux polysulfone membranes found a statistically significant difference in insulin levels between the two groups, with high-flux dialyzers producing a greater change. This translated into measurable improvements in insulin resistance among patients using high-flux filters, even in a short-term study. So while neither membrane type sends insulin into the dialysate, the high-flux membrane appears to adsorb more of it from the blood.
The Real Risk: Low Blood Sugar During Dialysis
For people with diabetes on dialysis, the practical concern isn’t whether insulin is being filtered out. It’s the risk of dangerously low blood sugar during treatment. This happens through a separate mechanism: glucose, which is much smaller than insulin, freely crosses the dialysis membrane. When glucose-free or low-glucose dialysate is used, plasma glucose rapidly diffuses down the concentration gradient from blood into the dialysate, draining sugar from the bloodstream.
On top of that, red blood cells consume extra glucose during hemodialysis. Changes in the internal pH of red blood cells during treatment accelerate their sugar-burning metabolism, pulling even more glucose out of the plasma. The combination of glucose loss into the dialysate and increased glucose consumption by red blood cells can cause blood sugar to drop below safe levels, sometimes severely. Using dialysate that contains glucose at concentrations of 5.55 mmol/L or higher reduces this risk substantially compared to glucose-free solutions.
Why Kidney Failure Changes Insulin Needs
The kidneys normally play a major role in clearing insulin from the body. When kidney function declines, insulin (both the body’s own and injected doses) lingers in the bloodstream longer than it should. This prolonged exposure means that the same dose of insulin has a stronger and longer-lasting effect in someone with advanced kidney disease than it would in someone with healthy kidneys.
This is why people with diabetes who start dialysis often need less insulin than before, not more. The most common clinical recommendation is to reduce basal insulin doses by up to 25% on dialysis days, though there is no firm consensus on the exact percentage. The reduction accounts for two overlapping effects: the decreased kidney clearance that was already present before dialysis started, and the additional glucose loss that occurs during the dialysis session itself.
Differences Between Insulin Types
Not all insulin products behave the same way in the setting of kidney failure. Regular human insulin and rapid-acting analogs like lispro show altered pharmacokinetics when kidney function is impaired, meaning they last longer and hit harder than expected. Some newer long-acting formulations have been designed with different clearance pathways. Insulin degludec, for example, has negligible renal clearance, and studies have confirmed that hemodialysis does not significantly affect its levels in the blood. This makes its dosing more predictable for people on dialysis, since the treatment session itself doesn’t create an additional variable.
For insulin types that do depend on the kidneys for clearance, the combination of reduced kidney function and the membrane adsorption effect during dialysis creates a complex dosing challenge. Blood sugar can swing unpredictably on dialysis days versus non-dialysis days, requiring careful monitoring and often different insulin doses depending on the schedule.
The Bottom Line on Dialyzability
Insulin is not dialyzable in the conventional sense. It does not pass through the membrane into the dialysate. It is, however, removed from the blood during hemodialysis through adsorption onto the membrane surface, with the amount varying by membrane type and flux rate. Polysulfone high-flux membranes remove the most. This distinction matters clinically because it means insulin removal during dialysis is somewhat unpredictable, depends on equipment choices, and is not something that can be precisely controlled by adjusting dialysis settings the way clearance of a truly dialyzable molecule can be.