Polyuria

Key Points Polyuria can result from too much fluid, too much solute, or too little arginine vasopressin.When diabetes insipidus (DI) is diagnosed, its cause must be determined.With central DI, other pituitary functions must be evaluated.A water deprivation test is the criterion standard for distinguishing among central DI, nephrogenic DI, and polydipsia.

Central Diabetes Insipidus in a Young Feline

Background: Central diabetes insipidus (CDI) is an endocrine disorder caused by the failure to produce, transport, or release ADH. This disease may show a primary etiology (idiopathic or congenital) or a secondary one (trauma or neoplasms). It is characterized by signs such as polyuria and polydipsia. The definitive diagnosis is obtained by the two-step water deprivation test; the absence of adequate urinary concentration in the first stage confirms the diagnosis of diabetes insipidus and, in the second stage, the response to the application of synthetic desmopressin confirms a central origin. Because CDI is rare in felines, the aim of this study was to report the occurrence of a case of CDI, probably of congenital primary origin, in an 8-month-old kitten.Case: An 8-month-old male feline, castrated, 3.2 kg, was brought to consultation with a report of polydipsia, polyuria, smaller size and weight, and lower activity when compared to his brother, for several months. On physical examination, lethargy, body score 2/5, and mild dehydration were noted, as well as deciduous teeth that should have already been replaced. Abdominal ultrasound and laboratory tests were requested, which ruled out chronic kidney disease (CKD), diabetes mellitus (DM), hyperadrenocorticism (HAC), and hyperthyroidism. Due to the fact that urinalysis evidenced hyposthenuria (urinary density [UD] 1.004), CDI was suspected. The patient underwent a water deprivation test and, after 7.5 h, lost 4.7% of his initial weight, while UD was 1.012, confirming the diagnosis of DI. The investigation then proceeded to the evaluation of the response to synthetic desmopressin by the application of 5 U IM. Two h later, UD was 1.019, confirming the diagnosis of CDI. The prescribed treatment was oral desmopressin at a dose of 100 μg BID. Upon return after 30 days, the feline had gained weight, was well hydrated, and the tutor reported higher activity. A new urinalysis showed a UD of 1.004 and inactive sediment. The tutor was asked to start administering the drug three times a day. However, noting that the patient’s quality of life had significantly improved, and wishing to spare the animal from the stress of taking medication once more a day, she chose not to modify the therapy and not to perform additional tests, due to financial limitation.Discussion: First, CKD, DM, HAC, and hyperthyroidism, more common conditions, were ruled out, and the investigation then proceeded to a water deprivation test. The feline lost 3% to 5% of the initial weight and UD was on the borderlinebetween hypo- and isosthenuria, as described in the literature for the diagnosis of DI. In the second stage of the test, slight urinary concentration was observed after the application of synthetic desmopressin, which confirmed the diagnosis of CDI. The dose of desmopressin prescribed for home treatment, 100 μg BID, was effective to relieve the clinical signs, but urine remained in hyposthenuria in the interval between administrations, suggesting that, for this patient, treatment would be more effective by administering the medication three times a day, in order to maintain an adequate serum concentration. Due to the diagnosis of CDI and the feline being young, the condition’s primary origin is believed to be congenital. It is also suspected that the patient may still have congenital hypothyroidism, due to the clinical signs of late tooth exchange and constant lethargy, in addition to laboratory results of thyroid hormones below reference levels. However, because thyroid tests were made by chemiluminescence, a repetition by radioimmunoassay is indicated. If hypothyroidism is confirmed,it would be possible to assume a common etiological factor between CDI and hypothyroidism, such as hypothalamicpituitary malformation.

EJE AWARD 2019: New diagnostic approaches for patients with polyuria polydipsia syndrome

Diabetes insipidus (DI), be it from central or nephrogenic origin, must be differentiated from secondary forms of hypotonic polyuria such as primary polydipsia. Differentiation is crucial since wrong treatment can have deleterious consequences. Since decades, the gold standard for differentiation has been the water deprivation test, which has limitations leading to an overall unsatisfying diagnostic accuracy. Furthermore, it is cumbersome for patients with a long test duration. Clinical signs and symptoms and MRI characteristics overlap between patients with DI and primary polydipsia. The direct test including vasopressin (AVP) measurement upon osmotic stimulation was meant to overcome these limitations, but failed to enter clinical practice mainly due to technical constraints of the AVP assay. Copeptin is secreted in equimolar amount to AVP but can easily be measured with a sandwich immunoassay. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation and has led to a ‘revival’ of the direct test in the differential diagnosis of DI. We have shown that a baseline copeptin, without prior thirsting, unequivocally identifies patients with nephrogenic DI. In contrast, for the differentiation between central DI and primary polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is superior to the water deprivation test. Close sodium monitoring during the test is a prerequisite. Further new test methods are currently evaluated and might provide an even simpler way of differential diagnosis in the future.

The water deprivation test and a potential role for the arginine vasopressin precursor copeptin to differentiate diabetes insipidus from primary polydipsia

The water deprivation test is the gold standard test to differentiate central or nephrogenic diabetes insipidus (DI) from primary polydipsia (PP) in patients with polyuria and polydipsia. Few studies have addressed the diagnostic performance of this test. The aim of this retrospective cohort study was to evaluate the diagnostic performance of the standard water deprivation test, including plasma arginine vasopressin (AVP) measurements, in 40 consecutive patients with polyuria. We compared initial test results with the final clinical diagnosis, i.e., no DI, central DI, or nephrogenic DI. The median length of follow-up was 8 years. In a subset of ten patients, the novel marker copeptin (CP) was measured in plasma. Using the final diagnosis as a gold standard, a threshold for urine osmolality of >800 mOsmol/kg after water deprivation yielded a sensitivity and specificity of 96 and 100%, respectively, for diagnosing PP. Sensitivity increased to 100% if the cut-off value for urine osmolality was set at 680 mOsmol/kg. Plasma AVP levels did not differ between patient groups and did not differentiate among central DI, nephrogenic DI, or PP. In all three patients with central DI, plasma CP was <2.5 pmol/l with plasma osmolality >290 mOsmol/kg, and >2.5 pmol/l in patients without DI. The optimal cut-off value for differentiating PP from DI during a water deprivation test was urine osmolality >680 mOsmol/kg. Differentiating between central and nephrogenic DI should be based on clinical judgment as AVP levels did not discriminate.