SHOULD WE TREAT AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE WITH AMLODIPINE?

S A BARTON1, S OZER1, K JIN QUEK1, O Z AMEER2, J K PHILLIPS1

1Department of Biomedical Science, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia, 2Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University, Riyadh, Kingdom of Saudi Arabia

Aim: To determine the impact of L-type calcium channel (LTCC) blockade with amlodipine, on progression of polycystic kidney disease (PKD) in a model of autosomal recessive PKD (ARPKD), the Lewis PKD (LPK) rat.
Background: LTCC blocker drugs are often prescribed to chronic kidney disease patients to control resistant hypertension. We have shown that amlodipine reduces blood pressure and improves vascular function in the LPK rat, however our results also demonstrated an increase in kidney-to-bodyweight ratio (K/BW).  Another LTCC blocker verapamil has been shown to increase cystic index in the Cy/+ rat model of autosomal dominant PKD and we therefore examined this parameter in the LPK animals.
Methods: Mixed-sex LPK rats (n=16) were allocated to treated (amlodipine 20 mg/kg/day p.o. 4-18 weeks) and vehicle groups. Following euthanasia, kidneys were dissected, weighed then fixed. H&E stained coronal kidney sections (4 µm) were prepared and whole-section images were acquired. The proportion of cystic-tissue; the cystic index (CI%), and the average cyst-area (CA) were determined using the analyse-particle function in ImageJ.
Results: Amlodipine treatment significantly increased the kidney weight (20.46±1.98 g vs. 15.05±1.77 g; P=0.04) and K/BW (8.93 0.45 % vs. 6.71±0.39 %; P<0.01) of LPK rats, but did not significantly affect bodyweight (228.25±17.27 g vs. 221.38±20.55 g), CI% (65.17±2.92 % vs. 65.74±1.50 %) or CA (0.25±0.01 mm2 vs. 0.26±0.01 mm2), all P>0.05.
Conclusion: Amlodipine increased the K/BW ratio however this was due to an overall increase in kidney weight rather than the measured cystic parameters (CI% and CA). Further research is required to elucidate the impact of LTCCs in the context of ARPKD.


Biography:
Sean recently completed a Master of Research at Macquarie University, where he investigated the mechanisms of chronic kidney disease (CKD) in the Lewis polycystic kidney disease rat model. He now works as a Research Assistant in the Autonomic and Sensory Neuroscience research group within the Department of Biomedical Sciences. In this role, he independently carries out physiological and molecular research projects, assists post-graduate students and supervises students on research rotations. His current work examines the underlying mechanisms that lead to hypertension and cardiovascular disease in association with CKD.

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