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Lithium Administration Can Attenuate the Progression of Polycystic Kidney Disease
Author(s) -
Kronk Trinity A.,
Himmel Nathaniel J.,
Mehran Nikki A.,
Blount Mitsi A.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1032.4
Subject(s) - polycystic kidney disease , kidney , medicine , lithium (medication) , endocrinology , cyst , kidney disease , renal function , autosomal dominant polycystic kidney disease , pathology
Polycystic kidney disease (PKD) is one of the most common genetic causes of renal decline and is characterized by the formation of fluid‐filled renal cysts that progressively expand to destroy normal kidney structure and function. Although PKD is the fourth leading cause of kidney failure in the US, there is no FDA‐approved pharmacological treatment; thus, many still regard PKD as an untreatable disease. Dysregulation of signaling pathways contribute to PKD including abnormally high production of renal cAMP. Because lithium can dampen renal cAMP synthesis and can be clinically administered with few complications, repurposing lithium as a treatment for the life‐long management of PKD is a viable and exciting new concept. Aged‐matched male Sprague‐Dawley (SD) and PCK rats (an orthologous model with physiological features that resemble human ADPKD) were pair‐fed a standard rodent diet supplemented with lithium carbonate (40 mmol/kg) for 2 weeks. SD and PCK rats pair‐fed an un‐supplemented, standard rodent diet were used as control groups. Following treatment, kidney/body weight, cyst number and cyst area were examined as indicators of cyst progression. Lithium‐treated PCK rats had lower kidney/body weight, fewer cysts and reduced average cyst area compared to untreated PCK rats. SD rats treated with lithium did not show a change in kidney weight compared to untreated SD rats. Compared to the SD untreated and SD lithium‐treated controls, GFR was slightly lower in untreated PCK rats; however, GFR was elevated in lithium‐treated PCK rats. A hallmark of renal damage, proteinuria, was observed in untreated PCK rats but the severity of proteinuria was dampened in lithium‐treated PCK rats. In conclusion, lithium treatment slows cyst progression in PCK rats and impedes the renal decline associated with progressing PKD, indicating that repurposing lithium may be an effective pharmacotherapy to attenuate advancing PKD.