Talphera (TLPH): KDIGO Draft Lists Nafamostat as CRRT Option

Talphera, Inc. (TLPH) told investors on August 12, 2026 that the draft KDIGO acute kidney injury guideline — the first rewrite of that document since 2012 — lists nafamostat, the anticoagulant it has in development, as an acceptable regional anticoagulant for continuous renal replacement therapy (CRRT) [1]. It is the only company this season to describe that guideline change as a commercial variable.

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How anticoagulation in ICU dialysis circuits went from house habit to a graded ranking

Continuous dialysis in an intensive care unit runs through an external blood circuit, and that circuit has to be anticoagulated to keep working. Acute kidney injury is a sharp drop in kidney function over hours to days, and critically ill patients are treated with CRRT, a dialysis that runs continuously at the bedside: blood is drawn out of the patient, passed through a filter, and returned. Blood clots once it leaves the vessel and blocks the filter and the tubing, so a drug is required. The usual approach is systemic heparin, which leaves the whole patient exposed to bleeding risk. The alternative, regional citrate anticoagulation, binds calcium only inside the external circuit to block clotting and replaces the calcium before the blood goes back in, so the patient is not anticoagulated systemically — but it requires constant monitoring and calcium replacement, and it is complicated to run.

There was no firm rule covering this step. KDIGO, the nonprofit that writes global kidney disease guidelines, used its 2012 edition only to suggest citrate over heparin at 2B strength for patients without contraindications, and to suggest heparin at 2C where citrate was contraindicated [2]. The number is the strength of the statement — 1 is a recommendation, 2 is a suggestion — and the letter is the quality of the evidence; 2B is not strong enough to make a hospital rewrite its treatment protocol. The 2026 draft raises citrate to a 1B recommendation and adds a separate ungraded practice point listing unfractionated heparin, epoprostenol and nafamostat mesylate as alternatives when citrate is contraindicated or unavailable [3]. A change like this travels to other hospitals because US pharmacy and nephrology committees need an external justification when they write treatment protocols, and a graded recommendation is that justification.

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The upgrade went to citrate, which most US ICUs do not currently use

The statement that gained strength in this draft is the one covering citrate. Citrate has the graded Recommendation 5.5.1, while nafamostat appears only in the ungraded practice point, so the two do not carry the same weight [3]. In the 2012 edition nafamostat appeared in no recommendation at all, and the text stated that it was used mainly in Japan and was not available in the USA or Europe [2].

Talphera's own management described what this recommendation runs into. The CEO said on the call that citrate is the only regional anticoagulant in use in the US today, that regional citrate is not FDA-approved for CRRT, and that it is complex to use and has other limitations, so most US sites do not write it into their CRRT protocols [1]. The chief medical officer gave the company's estimate that roughly 25% of US patients or hospitals use citrate and about 75% of institutions have no citrate available [1].

An independent measurement points the same way. A 2022 survey of 150 US nephrologists and intensivists found heparin used in about 43% of respondents' patients and citrate in 28%, with another 29% of patients receiving no anticoagulant at all during continuous dialysis [4]. Together those figures say the upgraded recommendation points at something most US hospitals are not doing today, so it calls for new protocols and new spending.

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A recurring per-patient-day cost, decided at only a few dozen institutions

That same survey carries the price tag for following the recommendation. It cites two cost studies: citrate anticoagulation ran about $221 more per day than heparin in one, and $389 more per day than non-citrate anticoagulation in the other, with the difference driven mainly by calcium monitoring, calcium replacement and the citrate itself [4]. This is a recurring cost measured per patient-day inside ICU operations, and the money goes to suppliers of citrate solutions, calcium products and continuous dialysis consumables.

The set of decision-makers is small. Talphera said that of roughly 200,000 US continuous dialysis procedures expected in 2027, more than half sit at about 70 institutions [1], which makes protocol committees at those institutions the audience. The company's press release that day mentioned only that the guideline references nafamostat as an acceptable regional anticoagulant, and said nothing about citrate gaining strength [5].

The boundary sits on the same chain. SeaStar Medical's (ICU) chief medical officer said on a May 13, 2026 call that many centers around the country have experience with citrate anticoagulation, and that a citrate protocol is a critical component of its own therapy [6] — which contradicts Talphera's account that 75% of institutions have no citrate, with the survey's 28% falling between the two. The guideline is also still a public review draft and has not been published in final form [3]. What can be checked later is whether the mix of citrate, heparin and no anticoagulant among US continuous dialysis patients shifts.

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Companies this change could affect:

• Baxter International Inc. (BAX): it supplies continuous renal replacement therapy machines and the consumables that go with them, so if citrate protocols do spread to more hospitals, the increment lands in tubing and solutions consumed per treatment day — the destination of the new cost line above. It has made no disclosure about this guideline change.
• Fresenius Medical Care AG & Co. KGaA (FMS): it provides dialysis products and services for hospital treatment of acute kidney failure, placing it on the same per-treatment-day supply chain, and it has likewise disclosed nothing about the change.

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Sources

[1] Drillr · Talphera (TLPH) · 2026-08-12 · FY2026 Q2 earnings call

"The only available regional anticoagulant being used in the U.S. today is citrate, yet regional citrate's not FDA-approved for CRRT, and it's also complex to use and has other limitations. As a result, most U.S. sites simply don't incorporate it into their CRRT protocols."

[2] KDIGO · Clinical Practice Guideline for Acute Kidney Injury (2012) · 2012-03 · clinical practice guideline · https://kdigo.org/wp-content/uploads/2016/10/KDIGO-2012-AKI-Guideline-English.pdf

[3] KDIGO · 2026 Clinical Practice Guideline for Acute Kidney Injury and Acute Kidney Disease, Public Review Draft · 2026-03 · draft clinical practice guideline · https://kdigo.org/wp-content/uploads/2026/03/KDIGO-2026-AKI-AKD-Guideline-Public-Review-Draft-March-2026.pdf

[4] Renal Failure · Anticoagulation practices for continuous renal replacement therapy: a survey of physicians from the United States · 2023-12 · peer-reviewed journal article · https://pmc.ncbi.nlm.nih.gov/articles/PMC11001369/

[5] PR Newswire · Talphera Announces Second Quarter 2026 Financial Results and Provides Corporate Update · 2026-08-12 · company press release · http://www.prnewswire.com/news-releases/talphera-announces-second-quarter-2026-financial-results-and-provides-corporate-update-302850056.html

[6] Drillr · SeaStar Medical (ICU) · 2026-05-13 · Q1 2026 earnings call

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