scott@vtx-cpd.com

Replying to Jane Sedgewick 15/04/2025 - 13:22

Hi Jane,

Lovely to see you at radiography rounds.

You are absolutely right that significant polyuria can lead to medullary washout, and this is an important consideration when interpreting the results of any water deprivation test or DDAVP trial. The rationale for recommending a DDAVP trial first (rather than starting with a formal water deprivation) is primarily related to safety and practicality:

In a patient with true CDI, the response to DDAVP is often quite striking even if there has been some degree of washout — typically you will still see a clear reduction in water intake and an increase in USG over the 3 to 5 day trial.

In contrast, psychogenic polydipsia (PP) cases, even if partial medullary washout is present, are much less likely to show a significant response to DDAVP alone. If they do respond, the magnitude is often partial or inconsistent.

If there is an equivocal response, a formal modified water deprivation test (MWDT) can still be considered afterward to distinguish partial CDI, PP, or medullary washout as the primary driver.

You are quite correct that gradual water restriction or hospitalization can sometimes help “re-set” the medullary concentration gradient. In practice, a period of 3–5 days of progressive water restriction (stage 1 of the MWDT) is intended to partially restore the renal medullary gradient. This improves the diagnostic utility of the subsequent dehydration phase. That said, hospitalization carries risks (stress potentially exacerbating psychogenic drinking, logistical challenges) which is why starting with a DDAVP trial at home has become a popular, safer first step, particularly when hospital monitoring isn’t ideal.

In terms of background:

Distinguishing CDI from PP can be very challenging because disorders of AVP secretion are recognized even in psychogenic polydipsia (e.g., altered set-point for AVP release, exaggerated or subnormal AVP responses). The natural pulsatility and variability of AVP secretion, combined with chronic over- or underhydration, further complicate interpretation.

A modified water deprivation test (MWDT) is time-consuming, requires rapid access to blood and urine analysis (especially sodium and BUN), and demands close observation to prevent hypertonic dehydration.

The MWDT typically consists of a three-stage process:

Gradual water restriction over 3–5 days to re-establish medullary gradients.

Complete water deprivation with careful monitoring for weight loss or rising USG.

DDAVP administration if USG fails to rise, to assess the response directly.

Pets with partial CDI show slight urine concentration with dehydration and a further increase following DDAVP. Pets with PP typically concentrate urine during the water restriction phase. Pets with complete CDI or NDI fail to concentrate until (or unless) given DDAVP.

Importantly, a therapeutic trial of DDAVP remains a practical alternative for many patients:

A dramatic reduction in water intake and increase in USG during a 5–7 day DDAVP trial is highly suggestive of CDI.

Failure to respond points toward primary NDI or psychogenic polydipsia.

This approach avoids the risks of acute hypertonic dehydration associated with MWDT and can be performed at home, making it far more practical and owner-friendly.

While rare, a note of caution: in psychogenic polydipsia cases, DDAVP can occasionally cause dilutional hyponatremia, so monitoring is still advised.

You raise an excellent point about the limitations of relying on total calcium (tCa) alone.

A useful reference on this topic is:

Tørnqvist-Johnsen C, Schnabel T, Gow AG, et al. Investigation of the relationship between ionised and total calcium in dogs with ionised hypercalcaemia. J Small Anim Pract. 2020;61(4):247-252. doi:10.1111/jsap.13109.
In this study, over one third of dogs with confirmed ionised hypercalcaemia had total calcium within the normal reference range, and importantly, most of these dogs had normal serum albumin.

This finding reinforces that early or modest ionized hypercalcemia (for example, due to malignancy or primary hyperparathyroidism) can be missed if relying only on total calcium values, even when albumin is normal.

So if clinical suspicion remains high (e.g., unexplained PU/PD, urolithiasis, azotaemia), it is worth pursuing ionized calcium testing if available, or at least repeating total calcium to monitor for evolution over time.

Thanks again for such excellent and thoughtful questions.

Best,

Scott 🙂