Clinical Studies
Hyperuricemia as a Clue for Central Diabetes Insipidus (Lack of V1 Effect) in the Differential Diagnosis of Polydipsia

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Abstract

PURPOSE: In the differential diagnosis of patients with polyuria-polydipsia one must distinguish usually between primary polydipsia (PP) and central diabetes insipidus (CDI). The first situation is a state of volume expansion and the second of volume contraction. We evaluate whether serum uric acid determination could help to differentiate between the two conditions.

PATIENTS AND METHODS: We analyzed the score of 13 consecutive patients with CDI, 7 patients with PP, and 7 patients with nephrogenic diabetes insipidus (NDI). Serum uric acid concentration was available during normonatremia without treatment with 1-desamino-8-D-arginine vasopressin (dDAVP), during mild dehydration and during treatment with dDAVP. In 8 of these patients plasma renin activity (PRA), urate, urea and creatinine clearances were also available. These data were also obtained in the patients with NDI. In 1 patient with CDI, we studied the effect on urate clearance of dDAVP, which stimulates exclusively the V2 receptors, and of triglycyl-lysine-vasopressin (TGLV), a potent V1-receptor agonist.

RESULTS: Normonatremic polydypsic patients with CDI presented an increase in uric acid concentration (7.1 ± 2.2 mg/dL), whereas in the PP group the value was decreased (3 ± 0.75 mg/dL; P <0.001). All the normonatremic PP presented a serum uric acid concentration lower than 5 mg/dL, whereas all the normonatremic CDI patients, exept 1, presented a value higher than 5 mg/dL. In both groups blood urea concentration was decreased as a consequence of high renal clearances. The hyperuricemia of CDI was related to low uric acid clearances. Patients with hypernatremia and NDI presented a lower increase in serum uric acid concentration than those with similar levels of hypernatremia and CDI (NDI: 5.7 ± 0.8 mg/dL and CDI: 7.9 ± 2.3 mg/dL; P <0.05) and the NDI patients presented an urate clearance corrected for creatinine clearance which was significantly higher than in CDI (9% ± 3% and 4% ± 1.1%; P <0.01). When the patients with CDI were treated with dDAVP and normalyzed their PRA (0.9 ± 0.4 ng/mL/h) we observed still mild hyperuricemia compared to controls (5.5 ± 1.4 mg/dL and 4.3 ± 0.9 mg/dL; P <0.01) and a low fractional excretion of filtered uric acid (6.5% ± 1.7% compared to 8.2% ± 2% in controls; P <0.05). Acute administration of dDAVP, stimulating the V2 receptors, in one patient with CDI, had no effect on urate clerance, while TGLV, which stimulates the V1 receptor, increased urate clearance.

CONCLUSION: The presence of an serum uric acid concentration higher than 5 mg/dL in polyuric polydipsic patients is highly suggestive of CDI. Even when these patients are treated with dDAVP many of them remain hyperuricemic, and this seems to be the consequence of a lack of V1 receptor stimulation.

Section snippets

Patients and Methods

We retrospectively analyzed the hospital records of all patients with severe chronic polyuria (>4 L/day) observed in our department over the last 10 years. Patients with a history of gout or alcohol abuse, or taking a medication known to interfere with uric acid metabolism were excluded.

In 13 patients with a diagnosis of central diabetes insipidus (CDI, group I) serum uric acid concentration was available in normonatremia (Na ≤ 145 mEq/L; while the patients were spontaneously taking a high

Results

All but 1 of the 13 patients with CDI (group I), presented a uric acid concentration higher than 5 mg/dL when normonatremic (see Fig. 1), whereas all the normonatremic PP patients presented a value lower than 5 mg/dL (mean value for CDI: 7.1 ± 2.2 mg/dL and 3 ± 0.75 mg/dL for the PP group; P <0.001) (see Table 1). Both groups presented lower blood urea concentration than controls (21 ± 7 mg/dl for CDI, P <0.01 and 22 ± 6 mg/dl for PP, P <0.05) and both presented high urea clearances. In the

Discussion

When intravenous fluid administration and osmotic diuresis, or different renal diseases (including potassium depletion or hypercalcemia) are excluded, the differential diagnosis of polyuria polydipsia must be made between primary polydipsia and diabetes insipidus either central (CDI) or nephrogenic (NDI). Our results suggest that hyperuricemia in a normonatremic polydipsic polyuric patient is highly suggestive of CDI.

In all our patients with PP and normonatremia, serum uric acid concentration

Acknowledgements

We are indebted to Dr G. Matte and Dr J. Unger for refering some of the patients.

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    This work was supported by a grant from the Fonds National de la Recherche Scientifique (FNRS) (1-5.193.96F)/(1-5.198.97F).

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