Ischemic heart disease cause of intradialytic hypertension in a patient with diabetic nephropathy

Abstract

A 73-year-old Japanese man was admitted with extreme intradialytic hypertension of four months’ duration that was refractory to antihypertensive agents. He had started hemodialysis five years previously because of diabetic nephropathy. Coronary angiography revealed coronary artery disease with significant stenosis of the left main trunk and the right coronary artery, and he underwent a coronary artery bypass graft. Thereafter, the intradialytic hypertension disappeared. Ischemic heart disease appears to be one cause of intradialytic hypertension.

<Learning objective: Intradialytic hypertension occurs in some patients with hemodialysis. Such patients are at increased risk for mortality and adverse cardiovascular events. Although the pathophysiological mechanisms remain unknown, ischemic heart disease appears to be one cause of intradialytic hypertension.>

Introduction

The blood pressure (BP) of most patients is lower at the end (postHD) than at the start (preHD) of hemodialysis (HD) and this is associated with fluid and salt removal. However, a higher postHD than preHD BP can occur and this is termed intradialytic hypertension [1], [2]. Such patients are at increased risk for mortality and adverse cardiovascular events [3], [4]{Park, 2018 #1505}. However, the pathophysiological mechanisms remain unknown.

We describe a patient with extremely high intradialytic hypertension that was ameliorated after coronary artery bypass surgery for coronary artery disease (CAD).

Case report

A 73-year-old Japanese man with intradialytic hypertension was admitted to our hospital. He had been started on HD five years previously because of diabetic nephropathy. His medical history included type 2 diabetes mellitus (DM), essential hypertension, paroxysmal atrial fibrillation, cerebral infarction, and atherosclerosis of the bilateral carotid arteries. The HD schedule comprised three 4-h sessions per week. He weighed 59 kg and the ultrafiltration volume was 1.6–1.8 kg per session. For about 4 years after starting HD, his blood pressure had been controlled and stable during dialysis treated with amlodipine 10 mg/day, azilsartan 20 mg/day, and guanabenz 2 mg.

However, his BP had increased to ≥ 200/80 mmHg during dialysis and this had persisted for four months.

He did not have chest pain, and ambulatory electrocardiography (ECG) and ECG during HD showed slight ST segment depression in leads V5-6 and left ventricular hypertrophy. Although the dry weight target weight at the end of HD gradually decreased to 57 kg, intradialytic hypertension continued. Thus, antihypertensive drugs had been changed and added. Finally, he had been medicated for hypertension with nifedipine CR 40 mg/day, azilsartan 40 mg/day, perindopril 4 mg/day, carvedilol 10 mg/day, and guanabenz 2 mg, and his office BP was around 140/90 mmHg.

He presented at a general hospital where contrast-enhanced computed tomography suggested stenosis of the left renal artery with calcification. He was then referred to our institution for evaluation and treatment of the intradialytic hypertension. Renovascular ultrasonography showed no significant finding of renovascular hypertension, and nifedipine CR of 20 mg/day was added to his medications. However, this was ineffective against the intradialytic hypertension (Fig. 1), and he was admitted to our institution.

Fig. 1.

Blood pressure after hemodialysis.

Average blood pressure increased from 152 ± 15/68 ± 6 mmHg to 173 ± 16/72 ± 5 mmHg before and after HD, respectively.

DBP, diastolic blood pressure; HD, hemodialysis; HR, heart rate; SBP, systolic blood pressure.

A physical examination upon admission revealed the following: BP 145/51 mmHg, heart rate 56 beats/min, weight 56.7 kg, and a Levine grade II systolic murmur at the apical region of heart.

Laboratory data showed normal including serum glucose and lipid profiles (fasting plasma glucose, 80 mg/dL; hemoglobin A1c, 6.0%; low-density lipoprotein cholesterol, 72 mg/dL; high-density lipoprotein cholesterol, 36 mg/dL; triglyceride, 69 mg/dL) except for renal dysfunction (creatinine, 9.5 mg/dL) and increase of N terminal-pro brain natriuretic peptide (NT-pro BNP) (>35,000 pg/mL). His blood hormonal examination to evaluate the cause of hypertension showed normal, and plasma renin activity (0.8 ng/mL/h) and aldosterone (34.6 pg/mL) did not increase during HD. Chest X-ray findings were normal with a cardiothoracic ratio of 46% and ECG showed sinus rhythm and left ventricular hypertrophy. Echocardiography showed left ventricular hypertrophy (interventricular septal thickness, 13 mm; left ventricular posterior wall thickness, 14 mm) with a normal left ventricular ejection fraction of 71%, diastolic dysfunction (lateral e’, 3.7 cm/s; lateral E/e’, 31.6), and moderate mitral regurgitation.

Other laboratory findings indicated the fluid volume was adequate for this patient (hemoglobin, 14.3 g/dL, diameters of inferior vena cava by echocardiography, 12 mm (expiratory phase), 5 mm (inspiratory phase) on admission).

Renal angiography showed 75% stenosis of the left renal artery. Coronary angiography showed 90% stenosis of the left main trunk and 99% stenosis of segment 1 in the right coronary artery (Fig. 2). Thus, he was treated by a coronary artery bypass graft (CABG), after which, the intradialytic hypertension disappeared (Fig. 3). We did not treat the renal artery stenosis at this time. He was discharged with systolic BP of ∼140/70 mmHg under medication with amlodipine 5 mg/day, azilsartan 20 mg/day, bisoprolol 1.25 mg/day, and doxazosin 2 mg/day. About 6 months after CABG, echocardiography demonstrated improvement of diastolic dysfunction (lateral e’, 7.6 cm/s; lateral E/e’, 8.7), and serum level of NT-pro BNP was decreased (9654 pg/mL) when he visited our outpatient clinic on a day without dialysis. Those suggested that this patient had had heart failure with preserved ejection fraction (HFpEF) before CABG.

Fig. 2.

Angiography findings. Renal angiography (A) shows 75% stenosis in left renal artery (arrow). Coronary angiography shows 90% and 99% stenosis of left main trunk (B) and segment 1 of right coronary artery (C), respectively.

Fig. 3.

Blood pressure before and after hemodialysis. Average blood pressure had no significant change from 146 ± 9/64 ± 5 to 146 ± 9/65 ± 3 mmHg after hemodialysis.

DBP, diastolic blood pressure; HD, hemodialysis; HR, heart rate; SBP, systolic blood pressure.

Discussion

The prevalence of intradialytic hypertension ranges from 5%–15% in patients on maintenance HD, depending on the definition [1], [2]. Most clinical investigations of intradialytic hypertension have used a range of definitions with varied thresholds of systolic BP (>10 mmHg) or mean arterial pressure (>15 mmHg). The United States Renal Data System, associates every increase in systolic BP of 10 mmHg during HD with a 6% increase in risk for death at 2 years [5]. In addition, more frequent intradialytic hypertension was incrementally associated with increased rates of 30-day morbidity and mortality [6]. Thus, our patient was at very high risk because his systolic BP increased by >50 mmHg during dialysis.

Although the pathophysiology is not fully understood, previous observational studies have shown that more advanced age, lower body weight, lower serum creatinine and albumin values, as well as medication with several antihypertensive agents are associated with intradialytic hypertension [7], [8]. Our patient was aged 73 years and he was medicated with several antihypertensive agents. Moreover, a cohort study demonstrated that patients with intradialytic hypertension had a higher prevalence of DM, ischemic heart disease, and congestive heart failure [8]. The present patient had severe CAD with HFpEF and DM, and the intradialytic hypertension and HFpEF improved after CABG with no change of DM control. These findings indicated that ischemic heart disease in association with HFpEF is one cause of intradialytic hypertension. We believe that this is the first confirmed case of an association between CAD and intradialytic hypertension.

However, we could not determine the mechanism of the intradialytic hypertension due to CAD because myocardial ischemia induces transient ventricular hypokinesis, i.e. myocardial stunning, that causes intra-dialytic hypotension. Although the precise pathophysiological mechanisms of intradialytic hypertension are obscure, hypotheses include volume overload, increasing vascular resistance, endothelial cell dysfunction, increased endothelin-1 values, discontinuation of antihypertensive agents, hypernatric dialysate, activation of the renin-angiotensin-aldosterone system, and sympathetic nervous system overactivation [4], [9]. HFpEF is related to many of those factors including sympathetic nerve activity increase [10]. It is not yet clear the relation between HFpEF and increased sympathetic nerve activity, oxygen species has been proposed as one of the important factors in HFpEF and sympathetic nerve activation as well as myocardial ischemia. Thus, myocardial ischemia during HD may have played an important pathogenic role to manifest intradialytic hypertension in our patient with HFpEF. Further study is needed to elucidate the incidence and mechanism of CAD-related intradialytic hypertension.

In conclusion, CAD should be considered when patients, particularly those with DM develop refractory intradialytic hypertension even though signs or symptoms of ischemic heart disease are absent.