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"
Janos Radó’s Reply on Janusz Rybakowski’s comment on his comment
Many thanks to Professor Rybakowski for his comment on my comment on Lin, Zhang, Feng, et al., “Aliskiren increases aquaporin-2 expression and attenuates lithium-induced nephrogenic diabetes insipidus.” Professor Rybakowski is well versed in my scientific profile and data as well as studies on lithium induced permanent nephrogenic diabetes insipidus. (Radó 2018, 2019a,b). His remarks in two previous papers (Rybakowski 2019a,b;) on my work is proof of this statement. Therefore, his present remarks and critique is of utmost significance.
The present therapy for lithium-induced nephrogenic diabetes insipidus in man is to counter anti-vasopressin action of lithium by administration of thiazide diuretics, antiprostaglandin compounds (indomethacine) combined with large doses of desmopressin. (Amiloride supplements the “present therapy” drug group). The “future” treatment seems to be (on the basis of recent animal experiments) to enhance the sensitivity of the kidney to vasopressin action by administering pharmacologic blockade of renal P2Y12 receptor. (Zhang, Pop, Carlson, Kishore 2012) On theoretical basis it is conceivable that the present therapy of lithium-induced nephrogenic insipidus perhaps could be combined with the “future” pharmacologic blockade. Administration of antagonists acting on the P2Y12 receptor, prasugral as well as clopidrogel completely suppressed lithium-induced polyuria and polydipsia in rats (Zhang, Peti-Peterdi, Brandes et al. 2017)
Pharmacologic blockade of renal P2Y12 receptor in rodents increases urinary concentrating ability by augmenting the effect of vasopressin on the kidney and ameliorates lithium-induced nephrogenic diabetes insipidus by potentiating the action of vasopressin on the renal collecting duct (Zhang Peti-Peterdi, Müller et al. 2015). This strategy may offer a novel and effective therapy for lithium-induced nephrogenic diabetes insipidus in man. Whether Aliskiren can belong in this group of antidiuretic medicines remains to be established.
Professor Rybakowsky declares that “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.” So, the clinical significance of Aliskiren in human lithium-induced nephrogenic diabetes insipidus should be determined in future studies.
Professor Rybakowsky writes that “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.”
However, the nephrogenic diabetes insipidus is reversible only in a part of lithium treated patients. In rare cases of lithium -induced nephrogenic diabetes insipidus withdrawal of lithium does not result in decrease of polyuria. In the so-called lithium-induced permanent nephrogenic diabetes insipidus polyuria does not change after interruption of lithium therapy.
On the basis of the available literature desmopressin alone and in combination with other antidiuretic drugs seemed to be an effective means in counteracting polyuria in patients with lithium-induced permanent nephrogenic diabetes insipidus (Radó 2019a).
We are all definitely convinced by the enormous work of Ban (2017), Blackwell (2014), Rybakowski (2017), Severus, Taylor, Sauer et al. (2014) and others that millions suffering from bipolar disorder need lithium treatment and making it safer by eliminating (at least partly) its most frequent side effect lithium polyuria, is a decent goal for both the investigators and physicians.
Thomas A. Ban: Neuropsychopharmacology in historical perspective. Education in the field in the post-psychopharmacology era. Collated 14. inhn.org.controversies. September 18, 2017.
Blackwell B. The Lithium Controversy: A Historical Autopsy. inhn.org.controversies. June 19, 2014.
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.
Radó J. Use of modern antidiuretic agents in the treatment of permanent lithium induced nephrogenic diabetes insipidus. (Administration of excessive doses of desmopressin resulted in clinically relevant antidiuresis, enhanced by indomethacine and abolished by calcitonine). (Janos Radó’s final comment on Barry Blackwell: The lithium controversy. A historical autopsy. Collated by Olaf Fjetland). January 25, 2018.
Radó J. Reply to Janusz Rybakowski’s commentary. Renal toxicity of Lithium in historical perspective with special reference to nephrogenic diabetes insipidus and its treatment. inhn.org.controversies. June 27, 2019.
Rybakowski J. Final comment: Half a Century of Inspiring Lithium Controversy (Barry Blackwell: The Lithium controversy: A historical autopsy. Collated by Olaf Fjetland). inhn.org.collated. September 30, 2017.
Rybakowski J. Commentary. Janos Radó. Renal toxicity of lithium in historical perspective with special reference to nephrogenic diabetes insipidus and its treatment. inhn.org.controversies. June 20, 2019a.
Rybakowski J. Response to Janos Radó’s reply (Janos Radó. Renal toxicity of lithium in historical perspective with special reference to nephrogenic diabetes insipidus and its treatment). inhn.org.controversies. November 14, 2019b.
Severus E, Taylor MJ, Sauer C, Pfennig A, Ritter P, Bauer M, Geddes JR. Lithium for prevention of mood episodes in bipolar disorders: systematic review and meta-analysis. Int J Bipolar Disord. 2014;2:15.
Zhang Y, Pop I, Carlson NG, Kishore BK. Genetic deletion of the P2Y12 receptor offers significant resistance to development of lithium-induced polyuria accompanied by alterations in PGE2 signaling. Am J Physiol Renal Physiol 2012;302: F70–F77.
Zhang Y, Peti-Peterdi J, Müller CE, Carlson NG, Baqi Y, Strasburg DL, Heiney KM, Villanueva K, Kohan DE, Kishore BK. P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus. J Am Soc Nephrol. 2015;26(12):2978-87.
Zhang Y, Peti-Peterdi J, Brandes A, Riquier-Brison A, Carlson NG, Müller CE, Ecelbarger CM, Kishore BK. Prasugral suppresses development of lithium-induced nephrogenic diabetes insipidus in mice. Purinergic Signal, 2017;13(2):239-48.
April 14, 2022