A hematocrit of 26% in a cat with kidney disease is no longer a number to watch. Under the 2026 IRIS revision it is close to a treatment trigger, and the newest drug for it is a daily oral liquid: molidustat, sold as Varenzin-CA1. In the field trial behind its approval, 68% of treated cats raised their hematocrit by at least 4 percentage points in 28 days, against 17% of cats on placebo.
The threshold moved to 25%, not 20%
For two decades the trigger for treating renal anemia was a packed cell volume under 20%. The 2026 IRIS recommendations split it into two tiers for cats: treat at HCT below 25%, and treat persistent anemia at 25–28%. The same document lists HIF-PH inhibitors such as molidustat alongside darbepoetin and transfusion.
Between 30% and 65% of cats with CKD develop anemia, and the share rises with stage: 4.8% at IRIS stage 2, 17.7% at stage 3 and 53.3% at stage 4 in one cohort. A PCV under 25% is an independent negative predictor of survival, and in stage 2 cats each 1% gain in PCV has been linked to a 10% lower risk of progression.
Why the kidney stops issuing the signal
Red cell production depends on erythropoietin, made by specialised renal cells that sense oxygen through hypoxia-inducible factor (HIF). In normal oxygen, prolyl hydroxylase marks HIF for destruction. In CKD two things fail at once: the EPO-producing cells die off, and the surviving kidney tissue consumes less oxygen, so HIF is destroyed even while the cat is anemic. Marrow output falls, and the anemia is non-regenerative: the marrow is fine, the order never arrives.
Iron is the second bottleneck. Inflammation raises hepcidin, which locks iron inside macrophages and blocks gut absorption, so a cat can be iron-deficient in function while its stores look adequate. That is why a HIF-PH inhibitor can underperform when iron status is never checked.
What the drug does and how a cycle runs
Molidustat is a competitive, reversible inhibitor of HIF prolyl hydroxylase. Blocking it lets HIF accumulate and the cat's own marrow respond. The label specifies a 25 mg/mL suspension at 5 mg/kg (0.2 mL/kg) once daily for up to 28 days, then at least 7 days off before a repeat cycle. Body weight is re-measured before each cycle; the volume rounds up to the next 0.1 mL. If the cat vomits part of a dose, it is not re-dosed that day. Renal excretion is negligible, so kidney function needs no dose change.
The bottle holds 27 mL and comes with a dosing syringe; the oil-based suspension must be shaken. In the long-term study, cats were re-treated once PCV fell below 28%, and the median gap between 28-day cycles was 11 to 18 days.
The 75-cat trial, in numbers
The field study enrolled 75 client-owned cats with PCV under 28% and creatinine above 1.8 mg/dL: 40 received molidustat, 35 a vehicle control, once daily for 28 days. Success meant a HCT rise of at least 4 points or 25% from baseline. On day 28, 68% of treated cats met it against 17% of controls (P < .001); on day 21 the split was 69% versus 24%. Mean HCT rose 5.25 points (±5.16) on treatment and fell 0.21 (±4.12) on placebo.
Pilot data agreed: 7 of 14 treated cats versus 1 of 6 controls. In the 20-week continuation phase, 64 cats received repeated cycles, and none reached a PCV of 45% in six months. Fourteen cats died or were euthanized during the 28-day phase, 6 treated and 8 control, all from progression of kidney disease.
What one cycle costs by weight
The 27 mL bottle listed at about $53 at US online pharmacies in November 2026. Volume scales with weight: a large cat needs a second bottle inside the first month.
| Cat weight | Daily volume | 28-day volume | Bottles | Drug cost |
|---|---|---|---|---|
| 3 kg | 0.6 mL | 16.8 mL | 1 | ~$53 |
| 4 kg | 0.8 mL | 22.4 mL | 1 | ~$53 |
| 5 kg | 1.0 mL | 28.0 mL | 2 | ~$107 |
Bloodwork is the other line item: a PCV or CBC before the cycle and once during it, plus the renal panel most CKD cats get every 3 months. Darbepoetin, by comparison, runs about $200 for a 25 µg/mL vial that supplies roughly 10 doses in a CKD cat, before the cost of clinic injections.
Darbepoetin, iron and transfusion
Darbepoetin is used off-label at 1 µg/kg subcutaneously once weekly, with PCV and blood pressure checked weekly until the 25–35% target, then injections every 2 to 3 weeks. Response rates run 60–65%, with a median of 3 weeks and a range of 1 to 6. Many vets now start with molidustat because of antibody-mediated pure red cell aplasia: 25–30% of cats given epoetin developed it, and it is less common but not absent with darbepoetin. Iron dextran at 50 mg per cat intramuscularly every 1 to 2 months is often added, because stimulated erythropoiesis uses iron faster than a CKD cat can mobilise it.
Transfusion has not gone away. It is right for a collapsed cat, or one breathing hard or symptomatic at a PCV near 15%, since it works in hours, not weeks. It is a bridge: transfused cells survive days to weeks in a uremic cat, and volume overload is a real risk.
Side effects and the monitoring that catches them
Vomiting is the most frequent complaint: 6 of 15 treated cats (40%) in the pilot, and 34.4% of all adverse events in the larger study, controls included. Systolic blood pressure and potassium can rise mildly, and the label records one suspected thromboembolism plus one seizure in a cat with a seizure history. HCT is checked during the cycle, and treatment stops at the top of the reference range. Phosphate binders and iron belong at least an hour apart, because multivalent cations chelate the drug. It is not for pregnant or breeding cats and has not been evaluated under 1 year of age.
The FDA cleared Varenzin-CA1 in May 2023 on a reasonable expectation of effectiveness, with continued study required — a lower bar than full approval, and the reason the 2026 long-term paper matters.
Five questions to settle before the first dose
- Is the anemia non-regenerative? A reticulocyte count answers it — see the PCV bands and reticulocyte line.
- Is something else driving it? Gut bleeding, iron deficiency and hyperthyroidism all worsen renal anemia, and an overactive thyroid can hide kidney disease.
- What is the IRIS stage and the trend across the last two checks? Staging decides how hard to push.
- What is the monitoring schedule, and at which HCT do we stop?
- What does the whole month cost, not just the bottle? CKD monthly costs add food, binders, fluids and bloodwork.
This article is information only and does not replace examination, diagnosis or prescription by a licensed veterinarian. Varenzin-CA1 is a prescription drug; doses, monitoring intervals and treatment decisions belong to the vet who has examined the cat and read its bloodwork.
Terms mentioned in this article
Frequently asked
My cat's HCT came back at 27%. Is that anemia?
It depends on the laboratory, and on the trend. Cornell gives 25–45% as the reference interval for cats, while many labs print 30–45%, so 27% is low-normal at best. IRIS 2026 says to treat at HCT below 25%, and to treat persistent anemia at 25–28%. A single 27% in a dehydrated cat can also overstate the red cell mass. Recheck in 2 to 4 weeks with a reticulocyte count before deciding anything.
Can molidustat be given with phosphate binders or iron?
Yes, but not at the same time. Multivalent cations such as calcium, iron, magnesium and aluminium chelate HIF-PH inhibitors, so the label advises giving the binder or iron supplement at least 1 hour apart from the dose. Shake the bottle, use the supplied syringe, and do not re-dose if the cat vomits part of it, because that day counts as dosed.
How long does a cat stay on Varenzin-CA1?
The labelled cycle is 28 consecutive days, then at least 7 days off. In the 2026 long-term study, cats were re-treated when PCV dropped below 28%, the median cycle was 28 days, and gaps between cycles ran 11 to 18 days; none reached a PCV of 45% over 6 months. HCT or PCV has to be checked during each cycle, and treatment stops if it reaches the top of the reference range.