Diabetes Insipidus

and SIADH: An

UpdateELI MCKENNA-WEISS, MD

KIDNEY CARE AND TRANSPLANT SERVICES OF NEW ENGLAND

I have no financial/advisory/research

conflicts of interest of any sort

SIADH

Uric acid handling in diagnosis

Uric acid level generally >5 mg/dL in hypovolemia

Uric acid level usually <4 mg/dL in SIADH

No clear pathogenesis of this

Diabetes Insipidus

Large volumes (>3 liters in 24 hours) of dilute urine (<300 mOsm/kg)

Central, partial central, nephrogenic, primary polydipsia

Gold standard for diagnosis currently the water deprivation test

New Possibilities in Diagnosis

Water deprivation is time consuming and unpleasant for patients

Runs the risk of causing dehydration prior to ddavp administration

In study recently published, this test correctly identified DI vs primary

polydipsia in 73% of patients

Copeptin

Copeptin is the C-terminal segment of argenine vasopressin prohormone

3% Saline administered until SNa was 150 (checked q30 min by POC), copeptin levels measured, then ddavp and free water administered to correct the abnormality

Patients reported this to be a less burdensome test

Equal numbers of adverse events

Correctly distinguished between the two conditions in 95% of the patients

Cases were reviewed after discharge with copeptin levels obscured. Clinical, historical and laboratory data reviewed by two investigators, a third was used in the rare occasion of a split vote

Wave of the future?

3% usually administered in intercare/step-down setting

POC testing expensive

Likely dangerous for a subset of patients (cirrhotics and CHF)

Unclear if copeptin test widely available

References

Boone, M., & Deen, P. M. (2008). Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption. European Journal of Physiology, 456, 1005-1024. https://doi.org/10.1007/s00424-008-0498-1

Burst, V., Grundmann, F., Kubacki, T., Greenberg, A., Becker, I., Rudolf, D., & Verbalis, J. (2017). Thiazide-associated hyponatremia, report of the hyponatremia registry: An observational multicenter international study. American Journal of Nephrology, 45, 420-430. https://doi.org/10.1159/000471493

Farmand, S., Lindh, J. D., Calissendorff, J., Skov, J., Falhammar, H., Nathanson, D., & Mannheimer, B. (2018). Differences in associations of antidepressants and hospitalization due to hyponatremia. The American Journal of Medicine, 131, 56-63. https://doi.org/10.1016/j.amjmed.2017.07.025

Fenske, W., Refardt, J., Chifu, I., Schnyder, I., Winzeler, B., Drummond, J., ... Christ-Crain, M. (2018). A copeptin-based approach in the diagnosis of diabetes insipidus. The New England Journal of Medicine, 379, 428-439. https://doi.org/10.1056/NEJMoa1803760

Fenske, W., Stork, S., Koschker, A., Blechschmidt, A., Lorenz, D., Wortmann, S., & Allolio, B. (2008). Value of fractional uric acid excretion in differential diagnosis of hyponatremic patients on diuretics. The Journal of Clinical Endocrinology and Metabolism, 93, 2991-2997. https://doi.org/10.1210/jc.2008-0330

Hoorn, E. J., & Zietse, R. (2017). Diagnosis and treatment of hyponatremia: Compilation of the guidelines. Journal of the American Society of Nephrology, 28, 1340-1349. https://doi.org/10.1681/ASN.2016101139

Milionis, H. J., Liamis, G. L., & Elisaf, M. S. (2002). The hyponatremic patient: a systematic approach to laboratory diagnosis. Canadian Medical Association Journal, 166(8), 1056-1062. Retrieved from Http://www.cmaj.ca

Soupart, A., Coffernils, M., Couturier, B., Gankam-Kengne, F., & Decaux, G. (2012, May). Efficacy and tolerance of urea compared with vaptans for long-term treatment of patients with SIADH. Clinical Journal of the American Society of Nephrology, 7, 742-747. https://doi.org/ 10.2215/CJN.06990711

Sterns, R. H., Silver, S. M., & Hix, J. K. (2015). Urea for hyponatremia? Kidney International, 87, 268-270. https://doi.org/10.1038/ki.2014.320