Janos Radó comment on the 2017 research article of Lin, Zhang, Feng et al., "Aliskiren increases aquaporin-2 expression and attenuates lithium-induced nephrogenic diabetes insipidus" 


Janusz Rybakowski’s comment


        The 2017 paper of Lin, Zhang, Feng et al. is interesting as it provides another possibility for treating lithium-induced polyuria: the direct renin inhibitor, aliskiren. However, I concur with Janos Radó’s statement that from the discovery that a new drug can abolish lithium-induced nephrogenic diabetes insipidus in animals to the administration in clinical practice is a long way.

        Although aliskiren upregulates AQP2 protein expression in inner medullary collecting duct principal cells and prevents lithium-induced nephrogenic diabetes insipidus in mice, there may be difficulties in the administration of this drug to humans where concomitant use of aliskiren with other agents acting on the renin-angiotensin system is associated with an increased risk of hypotension, hyperkalemia and changes in renal function (including acute renal failure). Furthermore, there are many medicines with which coadministration of aliskiren is strictly contraindicated or with which coadministration requires closely monitoring.

        From the practical point of view, the treatment of lithium-induced polyuria makes sense if the polyuria is not very severe and does not improve after the reduction of the lithium dose. In such a situation, the measures provided by Radó (2019a,b) such as thiazide diuretics, non-steroid anti-inflammatory drugs, amiloride, and desmopressin or their combinations can be tried.

        If the polyuria reaches the intensity of diabetes insipidus, the best recommendation is lithium discontinuation.



Lin Y, Zhang T, Feng P, Qiu M, Liu Q, Li S, Zheng P, Kong Y, Levi M, Li C, Wang W.  Aliskiren increases aquaporin-2 expression and attenuates lithium-induced nephrogenic diabetes insipidus. Am J Physiol Renal Physiol, 2017;313:F914-25.

Radó J. Desmopressin may counteract polyuria in lithium-induced nephrogenic diabetes insipidus (Review of the literature). inhn.org.controversies. June 27, 2019a

Radó J. Renal Toxicity of Lithium in Historical Perspective with Special Reference To Nephrogenic Diabetes Insipidus and its Treatment. inhn.org.controversies. May 2, 2019b.


July 1, 2021