Hypertension with Kidney Failure

Patient A 62-year-old woman with a history of kidney failure secondary to polycystic kidney disease treated with hemodialysis (HD) for 2 years presents for her regular dialysis treatment. She currently dialyzes via a left upper extremity arteriovenous fistula and no longer makes urine. Her predialysis BP is 172/94 mm Hg. Her weight is 72 kg. On repeat 5 minutes later after she relaxes, her BP is 170/92 mm Hg. Her dialysis treatment is initiated per her regular prescription for 4 hours with 2-L ultrafiltration to achieve a target estimated dry weight of 69 kg. At the end of the treatment, her postdialysis BP is 160/84 mm Hg. When she returns for her next dialysis session, her predialysis BP is again high at 176/90 mm Hg. Her current BP-lowering medications are amlodipine at 10 mg daily, carvedilol at 25 mg twice a day, and hydralazine at 25 mg twice a day. She states that her BP was lower the day before during a visit to her cardiologist. She measures her home BPs intermittently as well. Question 1 Which BP measurement should you treat in this patient? A. Predialysis BP B. Clinic BP C. Postdialysis BP D. Home BP Discussion of Question 1 Hypertension is one of the most important modifiable risk factors for cardiovascular disease events and death in patients treated with HD. Unique to patients on HD, the temporality of the BP measurement in relation to dialysis is important. Measurements of BP at dialysis versus those on a nondialysis day can differ substantially, are poorly correlated, and have differential associations with outcomes (1,2). Observational studies in patients on HD have demonstrated a “U-shaped association,” in which high and low pre- and postdialysis systolic BP measurements are both associated with increased risk of mortality (3). More specifically, predialysis systolic BP of <140 mm Hg is associated with higher risk of mortality compared with systolic BP >140 mm Hg (1,3). Patients with high predialysis systolic BP (e.g., 150–179 mm Hg) seem to be at lower risk for death compared with those with predialysis systolic BP of 140–149 mm Hg. Similar findings have been observed for postdialysis systolic BP. These U-shaped paradoxes conflict with data seen in the general adult population and in individuals with CKD, and they may lead to permissive hypertension. Moreover, there are poor correlations of predialysis and postdialysis BP overall with “gold standard” ambulatory BP monitoring (2). Therefore, answers A and C are incorrect. Alternatively, data support treating out-of-dialysis-unit BP, which has a linear, direct association with risk of cardiovascular disease and death in patients on HD, where higher BP is associated with higher risk of death (1). Both clinic BP (answer B) and home BP (answer D) can be measured on nondialysis days. However, home BP offers certain advantages over clinic BPs. There are strong data validating home BP measurements in patients on dialysis with 44-hour interdialytic ambulatory BPs as well as clinical outcomes (4). Home BP measurement eliminates possible “white coat” effect and captures multiple measurements over several days; thus, it provides better assessment of overall BP control. Providing care outside the health care setting has been linked to improved patient engagement, particularly with increased adoption of mobile health technologies (5). Interdialytic ambulatory BP monitoring would also be reasonable in this case and is the “gold standard.” Given the listed options, the best answer is D. However, it should be acknowledged that further randomized clinical trials are needed to implement home BP into practice as there are still gaps in knowledge, including home BP targets, effect of treating home BP on clinical outcomes, and pragmatic strategies for implementation. Patient Continued You ask the patient to take her home BPs on nondialysis days. She brings in a BP log 2 weeks later; her mean home systolic BP is 162 mm Hg, and her mean home diastolic BP is 86 mm Hg. To treat her hypertension, you adjust her target dry weight from 69 to 68 kg. At her next dialysis session with the newly prescribed dry weight, her systolic BP drops by 30 mm Hg within 60 minutes of dialysis initiation, and she complains of lightheadedness. Her ultrafiltration is turned off, but her BP remains low; she is given a bolus of 250 ml of normal saline. Her BP increases, and she completes her dialysis treatment without further ultrafiltration or symptoms. However, you are concerned about her episode of intradialytic hypotension. Question 2 Which of the following is not a consequence of intradialytic hypotension? A. Myocardial stunning B. Decreased solute clearance C. Decreased cerebral perfusion D. Mesenteric ischemia E. Higher risk of mortality Discussion of Question 2 Intradialytic hypotension is a common complication of HD, occurring in 10%–70% of HD treatments (6). Intradialytic hypotension occurs when the rate of volume removal during HD exceeds the ability of the patient’s inherent plasma refill rate and compensatory cardiovascular responses to maintain an adequate BP. These compensatory responses include increasing heart rate and cardiac stroke volume to maintain cardiac output, enhanced venoconstriction to maintain cardiac preload, and augmenting arterial vasoconstriction to increase systemic vascular resistance. From a clinical perspective, intradialytic hypotension may occur for a variety of reasons, including those related to the dialysis prescription or the dialysis procedure itself. Examples include a prescribed target weight that is too low, resulting in an excessive total ultrafiltration volume. Alternatively, the target weight may be correct, but high interdialytic weight gain by the patient may result in an excessively high hourly weight-based ultrafiltration rate. Despite its high prevalence, there is no consensus definition for intradialytic hypotension. The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative and the European Best Practice Guidelines both define intradialytic hypotension as a fall in systolic BP by ≥20 mm Hg or a fall in mean arterial pressure by ≥10 mm Hg accompanied by the presence of symptoms attributable to low BP. In contrast, other definitions are on the basis of the presence of a nadir intradialytic BP below a certain value, such as 90, 95, or 100 mm Hg. In general, nadir-based definitions have been shown to more accurately predict subsequent adverse outcomes relative to definitions on the basis of a fall in systolic BP (6). Intradialytic hypotension in patients undergoing maintenance HD has been shown to be linked with a wide range of adverse clinical outcomes. Perhaps most concerning is the demonstrated association of intradialytic hypotension with increased risk for all-cause and cardiovascular death. For example, observational studies have demonstrated that patients experiencing intradialytic hypotension, defined by a nadir systolic BP <90 mm Hg in ≥30% of HD treatments, have a 30%–50% increase in the risk of all-cause mortality in the subsequent 2 years compared with patients without intradialytic hypotension (6). Thus, answer E is not correct. Data also strongly support the association of intradialytic hypotension with other intermediate outcomes that represent important end organ effects of decreased organ perfusion. Studies have shown a direct and linear association between the proportion of HD treatments in which systolic BP dropped to <90 mm Hg and the odds of hospitalization for mesenteric ischemia (7). Thus, answer D is not correct. Higher ultrafiltration volumes and lower intradialytic BP are strongly associated with a decline in intradialytic cerebral blood flow, lower white matter and hippocampal volume on magnetic resonance imaging, and lower scores on standardized measures of global cognitive function (8). Thus, answer C is incorrect. Furthermore, ultrafiltration volume and intradialytic hypotension have been shown to be independent determinants of regional cardiac wall motion abnormalities and myocardial stunning in intradialytic echocardiographic studies. Myocardial stunning as detected by serial intradialytic echocardiography has also been shown to be associated with increased 1-year mortality among patients on prevalent HD (9). Thus, answer A is not correct. In contrast to the aforementioned complications, there is no compelling evidence that lower BPs during HD or episodes of intradialytic hypotension lead to reduced dialytic solute clearance. In fact, a post hoc analysis of the Hemodialysis study showed that patients with higher Kt/V had a greater frequency of intradialytic hypotensive events (10). One hypothesis for this observation is that greater solute clearance resulted in larger intradialytic plasma osmolality decline, which subsequently increased risk for intradialytic hypotension events. Therefore, the best answer for this question is B. Despite the association of intradialytic hypotension with multiple adverse effects, there remains uncertainty around how and whether specific modifications in dialysis treatment parameters or pharmacotherapy to reduce the incidence of intradialytic hypotensive episodes may lead to improved clinical outcomes for patients. In patients who experience recurrent intradialytic hypotension without obvious extracellular volume excess on examination, attention should certainly be paid to whether the target weight may need to be adjusted upward or whether the timing of any predialysis antihypertensive medications may need to be altered. In patients who are chronically over their target dry weight, target dry weight should be carefully lowered. In patients with large intradialytic weight gains for whom intradialytic hypotension accompanies high hourly ultrafiltration rates, attention should be directed at dietary sodium restriction to lower weight gains and toward consideration of adjusting the duration or frequency of HD sessions to achieve lower hourly ultrafiltration rates. However, further research on the prevention and treatment of intradialytic hypotension is needed to improve quality of life and clinical outcomes for patients undergoing HD. Disclosures N. Bansal reports serving as an associate editor of Kidney360. M.B. Rivara reports serving on the CJASN editorial board and the Northwest Kidney Centers Medical Executive Committee and reports research funding from Satellite Healthcare.