Abstract

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and fourth case of kidney failure worldwide. Treatment options for ADPKD include therapy with vasopressin (ADH) receptor 2 antagonist, nephroprotection, and eventually renal replacement therapy. The earliest and most prevalent systemic complication of ADPKD is hypertension. The pathogenesis of hypertension in ADPKD is multifactorial, including endothelial dysfunction and activation of renin-angiotensin-aldosterone system (RAAS). Antihypertensive therapy with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is expected to decrease the left ventricular hypertrophy and proteinuria in ADPKD patients, according to HALT-PKD study. Data about preferences of second choice therapy and safety of other medications is lacking. Diuretics are commonly prescribed drugs in essential hypertension but carry risk of provoking ADH stimulation that may be potentially harmful in ADPKD because ADH stimulates cyst proliferation. We analyzed real-life data on antihypertensive prescriptions to determine and compare trends in treatment of hypertension in ADPKD patients in Poland and Japan. Method Patterns of antihypertensive prescriptions of ACEi, ARB, and diuretics were analyzed in patients from Poland (n = 131, median age 40 years; data 2014-2019) and Japan (n = 180, median age 44 years, data 2005-2017) diagnosed with ADPKD. The number of different medications used in combination was counted. For diuretics, even if multiple diuretics were used, they were counted as a single item. Furthermore, combination drug products were decomposed into their individual components, which were counted as either antihypertensive drugs or diuretics, respectively. Results The patterns of the number of prescriptions of antihypertensive drugs were similar in the two countries, see Figure 1. In Polish patients, the commonest pattern was no antihypertensive drugs (45.0%), followed by one (28.2%), two (16.8%), three (9.2%), and four (0.8%) prescriptions. In Japanese patients, the corresponding figures were: no antihypertensive drugs (41.1%), followed by one (32.2%), two (20.6%), three (4.4%), and four (1.7%) prescriptions in decreasing order. ACEi and ARBs were used for more than half of the patients, both Polish and Japanese. The utilization of ACEi/ARB in Polish individuals as a first-choice medication was 78.4% (75.0% in men, 81.0% in women) while in Japan 65.5% (66.7% in men, 63.2% in women). When patients were prescribed 3 or more antihypertensive drugs, ACEi/ARB was chosen in 100%, in both countries. Regarding diuretics, 15.3% of Polish patients and 6.7% of Japanese patients used them. Among patients who had one antihypertensive drug, 7.6% of Polish and 2.2% of Japanese patients also used diuretics. 44.2% of Polish and 38.9% of Japanese did not use either antihypertensive drugs or diuretics. Conclusion The patterns of number of prescriptions of antihypertensive drugs were similar among ADPKD patients in Poland and Japan while the use of diuretics was more common in Polish than in Japanese patients. In both countries, ACEi/ARB was the most frequent choice, which is in concordance with current recommendations. Unexpectedly, anti-RAAS were as frequently prescribed in women than in men, suggesting that the teratogenicity risk of the drugs did not limit access to the benefits of the treatment in both sexes.

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