Hyperuricemia as a Clue for Central Diabetes Insipidus (Lack of V1 Effect) in the Differential Diagnosis of Polydipsia
|Title:||Hyperuricemia as a Clue for Central Diabetes Insipidus (Lack of V1 Effect) in the Differential Diagnosis of Polydipsia|
|Authors:||Decaux, M.D., Ph.D., Guy; Prospert, M.D., Fernand; Namias, M.D., Bernard; Soupart, M.D., Alain|
|Publisher:||American Journal of Medicine|
|Date Published:||November 01, 1997|
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, except 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 clearance, while TGLV, which stimulates the V1 receptor, increased urate clearance.
CONCLUSION: The presence of a 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.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
Diagnosing the distinction between PP and either form of DI can be tricky. PP is associated with an increase of body fluid which can lead to a deficit of blood sodium. DI is associated with body fluid depletion which can lead to excessive blood sodium. However, both PP and DI are associated with a deficit of blood urea because so much urea is excreted due to excessive urination. Decaux, et al., hypothesize that blood levels of uric acid might provide a way to distinguish between PP and DI.
Uric acid excretion is influenced by blood fluid volume. When there is an excess (as in PP), uric acid has higher rates of excretion, leading to a decrease of uric acid concentration in the blood. When there is blood volume contraction (as in CDI), there is reduced uric acid excretion, leading to an excessive concentration of uric acid in the blood. The authors reasoned that the excess of blood uric acid commonly recorded in CDI patients could help to distinguish these patients from patients with PP. They analyzed the hospital records of all patients with severe chronic polyuria observed in their department over the last ten years.
All but one of the 13 patients with CDI had a higher uric acid concentration than the PP patients. This was when both groups were in a state where their blood sodium levels were in the normal range. This indicates that uric acid levels in the blood can be used to distinguish between patients with CDI and PP. Both groups had lower blood urea concentrations than the control group. And both had high urea excretion levels due to their excessive urination.
The fact that CDI patients often retain high blood levels of uric acid even after being successfully treated requires some explanation. CDI occurs when the body produces insufficient amounts of the antidiuretic hormone, arginine vasopressin (AVP). Normally, AVP binds with the vasopressin-2 receptor (V2R) in kidney cells. This sets off a cascade of molecular events which enable the kidneys to concentrate urine and maintain body water balance. When there is no AVP there is nothing to bind with V2R and begin the molecular events that lead to urine concentration and body water balance. CDI patients are treated by administering a synthetic derivative of AVP called DDAVP. However, DDAVP only stimulates the vasopressin-2 receptor, not the vasopressin-1 receptor which, the authors speculate, has something to do with uric acid excretion.