The Effects of Antihypertensive Agents on the Survival Rate of Polycystic Kideney Disease in Han: SPRD Rats.

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder in humans. Hypertension is one of the major complications, and its control might affect the renal survival and disease mortality. Suitable antihypertensive agents have been discussed based on clinical and animal studies, but no definitive conclusion has been reached. Generally, therefore, all antihypertensives are indiscriminately treated as if providing the same level of blood pressure control. In this study, the blood pressure control of two antihypertensives was investigated using a rat model of ADPKD in humans. Twenty-four male Hannover-Sprague Dawley (Han:SPRD) rats were divided into three groups: a group receiving amlodipine (6 mg/day), a group receiving benazepril (6 mg/day) and an untreated control group. Blood pressure, body weight, and urinary protein excretion were regularly measured up to week 52. Amlodipine and benazepril significantly decreased blood pressure and urinary protein excretion to the same degree. Moreover, a remarkably prolonged survival rate was observed in both groups (at week 52, the survival rate was 25% in controls, 50% in the amlodipine group, and 50% in the benazepril group). Examination at autopsy revealed that enlarged cysts were prevalent in the renal tissue of both experimental all three groups, suggesting that the cystic disease had reached the end-stage in all the animals. In conclusion, both amlodipine and benazepril significantly improved blood pressure control, urinary protein excretion, and survival rate, possibly due to their enhancement of renal survival.

PKD1 haploinsufficiency is associated with altered vascular reactivity and abnormal calcium signaling in the mouse aorta

“…Using tail-cuff plethysmography, mild hypertension was detected in Pkd1 +/− mice aged 30 weeks. Increased SBP measured by the same method has been reported in 20-week-old Han/SPRD rats [14]. The hands-off measurement of blood pressure using telemetry revealed that, in stressfree animals, blood pressure was similar in Pkd1 +/+ and Pkd1 +/− mice.…”

Rosiglitazone attenuates development of polycystic kidney disease and prolongs survival in Han:SPRD rats

“…Until now, several drugs have proven effective in Han:SPRD rats, but most of these studies were short-term observations, among which only two studies reported a survival time [16,28]. The present study demonstrates that rosiglitazone had short-term therapeutic effects in Han:SPRD rats in multiple experiments.…”

Clinical effects of calcium channel blockers and renin-angiotensin-aldosterone system inhibitors on changes in the estimated glomerular filtration rate in patients with polycystic kidney disease

“…High blood pressure is the most important risk factor in patients with ADPKD; clinically, uncontrolled hypertension leads to a deterioration of renal function in ADPKD patients [10]. Higashikuni et al [11] reported that even in individuals without hypertension, the risk of albuminuria decreased in parallel with decreasing blood pressure in chronic kidney disease (CKD) patients.…”