Copeptin Role in the Diabetes Insipidus Work Up: A Case of Nephrogenic DI Diagnosed by Copeptin Levels After Indeterminate Results on Water Deprivation Test

Introduction:
The indirect water-deprivation test (WDT) is the gold standard for the diagnosis of diabetes insipidus (DI). This test can be technically cumbersome and inaccurate. Because Copeptin and Argine Vasopressin (AVP) are derived from the same precursor protein, pre-provasopressin, copeptin provides the advantage of a better diagnostic marker. We present a case of DI where copeptin elucidated the diagnosis.

Case Description:
A 66 y/o male with past medical history of bipolar disorder (20 years taking lithium, last use 2 years prior), hypertension, chronic kidney disease stage 3, head trauma 10 years prior. He was sent to the ER from a psychiatry facility for urinary and fecal incontinence. History is significant for polyuria, and polydipsia (~3 liters of water/day). No headaches, or vision changes. Unremarkable physical exam including mental status. Labs showed sodium of 152; urine osm 260; serum osm 309, and urinary sodium 68; baseline creatinine 1.5 with GFR 55. CT head w/o contrast was negative. Hypernatremia improved with D5W solution. Urine output was difficult to calculate given urinary incontinence. Endocrinology was consulted for DI work-up.

The patient was transferred to the ICU for a WDT. Foley catheter was placed. The starting sodium level was 145. One hour later, sodium went up to 147 with plasma osm of 304. A copeptin level was sent. He received 2mcg of DDAVP IV. The urine osm was checked every 30 min for 2 hours. Results showed urine osmolarity levels of 304, 320, 346 and 346 post-DDAVP. Sodium remained unchanged at a level of 148 pointing to nephrogenic DI. He was started on HCTZ 25mg PO daily with normal sodium levels at 24 hours without IV fluids. Copeptin resulted at 26 pmol/L confirming a diagnosis of complete nephrogenic DI.

Discussion:
Our patient had risk factors for central and nephrogenic DI. WDT was performed with an increase of <15% in uOsm with persistently high sodium despite DDAVP ruling out central DI. This minimal response pointed to complete Nephrogenic DI; however, persistent urine osm >300 left partial central DI possible. The copeptin level of 26 confirmed the diagnosis of complete nephrogenic DI. Diagnostic accuracy of the classical WDT is only around 70%. Multiple studies have evaluated the accuracy of copeptin in the differential diagnosis of polyuria-polydipsia syndrome showing a single baseline copeptin level >21.4 pmol/L differentiated nephrogenic DI from other etiologies with a 100% sensitivity and specificity (1). The superiority of copeptin has also been confirmed when applies to hypertonic saline-stimulated testing (2). Copeptin is a more stable, reliable, and rapidly measurable blood biomarker of AVP. The use of copeptin should become standard of care for all DI work-up.