- Email: [email protected]
Hypertension in hemodialysis patients: More questions than answers
Hypertension in Hemodialysis Patients: More Questions Than Answers Kent A. Kirchner, MD
H
YPERTENSION is prevalent in patients undergoing chronic dialysis and is likely a significant contributor to the high cardiovascular death rate in the end-stage renal disease (ESRD) population.‘-6 Initial assessments of the mechanisms causing hypertension in the ESRD population concluded that sodium or fluid overload was responsible for elevated blood pressure in 90% of cases, whereas the remaining 10% had elevated plasma renin activities.7-9 Indeed, the concept of using a decrease in blood pressure as the indicator for optimal or dry weight is based on the assumption that elevated blood pressure in hemodialysis patients is primarily the result of sodium or fluid overload. Registry data from Europe showing that 83% of their dialysis population requires blood pressure medications and observations in this country that blood pressure is inadequately controlled in 50% to 85% of presumably adequately dialyzed patients have challenged the dictum that sodium or fluid overload is the seminal mechanism for hypertension in most patients requiring maintenance hemodialysis. This controversy is reflected in the conclusions of two manuscripts published in this issue of the Journal.
Luik et al,” examining the effects of modest changes in vascular volume on interdialytic blood pressure, found no correlation between fluid load or weight gain and interdialytic blood pressure in 10 chronic hemodialysis patients, four of whom had been on antihypertensive therapy before selection for study.” Hypervolemia in this study increased cardiac index and tended to reduce total peripheral resistance index in association with significant reductions in plasma levels of arginine vasopressin and angiotensin II. There was also an increase in atria1 natriuretic factor. The changes reported in these hemodialysis patients are similar to the initial changes observed in experimental animals or humans with normal renal function given a volume challenge. The investigators thus document that the shortand intermediate-term physiological mechanisms essential for buffering direct effects of fluid loads on mean arterial pressure are intact in many hemodialysis patients. Studies examining the relaAmerican
Journal
of Kidney
Diseases,
Vol 30, No 4 (October),
tionship between changes in vascular volume and blood pressure in animals have shown the power of these mechanisms, which when fully operational allow the circulation to absorb up to a 30% increase in blood volume over a period of 4 minutes with minimal change in mean arterial pressure.” Impairment of these mechanisms leads to increased susceptibility to volume-induced hypertension. This observation is reflected in the study by Luik et al, in which hemodialysis patients in whom hypervolemia was associated with increasing interdialytic blood pressure showed less hypervolemia-induced suppression of plasma renin and angiotensin. The findings reported by Luik et al are consistent with earlier observations recorded by Kim et al,‘* who found that sodium and water loading increases blood pressure in chronic hemodialysis patients only in circumstances in which the total peripheral resistance index fails to decrease.” Events that impair ability to reduce total peripheral resistance might include not only failure to suppress renin or angiotensin II, but also abnormal baroreflex sensitivity, increased activation of the sympathetic nervous system, circulating inhibitors of the nitric oxide system, and reduced production or release of prostaglandin and renomedullary lipids. In the presence of such abnormalities, hemodialysis patients may be sensitized to effects of even small increments in vascular volume. An opposite conclusion regarding the role of fluid overload in the development of hypertension in hemodialysis patients was noted in the study reported in this issue of the Journal by Katzarski et a1.13 While evaluating ultrasound measurements of inferior vena cava diameter (IVCD) as a method to assess dry weight in hemodialysis patients, they observed that blood volume correlated with mean arterial pressure both before and after the hemodialysis procedure. Blood volume was higher in hypertensive hemodialysis patients compared with normotensive hemodialysis patients at equivalent body weights both before and after hemodialysis. This observa0 1997 by the National Kidney 0272-6386/97/3004-0022$3.00/O 1997:
pp 577-578
Foundation,
Inc.
577
578
tion suggests that the relationship between plasma volume and weight may be different in hypertensive hemodialysis patients compared with normotensive hemodialysis patients. Measurement of IVCD during or within 2 hours after the dialysis procedure did not increase the accuracy of assessing dry weight. Both IVCD and blood volume increased for several hours after the hemodialysis procedure, presumably as a result of fluid shifts between extravascular and intravascular space. These changes seemed to be more marked in hypertensive hemodialysis patients. The postdialysis increase in IVCD and blood volume could be lessened by increasing dialysis time from 3 to 6 hours, even though postdialysis weights were equivalent in both circumstances. The investigators interpreted their findings as support for the hypothesis that fluid overload plays an important role in the pathogenesis hypertension in hemodialysis patients. Interestingly, mean arterial pressure was not normalized by fluid removal in their hypertensive dialysis patients. Furthermore, if the blood volumes measured in group A patients are representative of their entire study population, their data also suggest that dialysis patients with hypertension remain hypertensive even after their blood volume is reduced to values not different from those found predialysis in normotensives or in healthy subjects. This implies that sodium/fluid overload is not the only factor maintaining elevated blood pressure in the hypertensive hemodialysis patients. Clearly, further investigation will be required to fully elucidate mechanisms contributing to the development and maintenance of hypertension in hemodialysis patients. The available data do not convincingly mandate a change in the approach currently used to manage hypertension in the ESRD population. The impressive blood pressure control and survival data reported from the Centre de Rein Artificiel in Tassin, France, show what is achievable, although their dialysis prescription of three 8-hour sessions per week is, in my experience, unacceptable to most patients receiving hemodialysis in the United States. The challenge for nephrologists in this country is to
KENT
A. KIRCHNER
determine whether similar outcomes can be achieved through other alterations in dialysis technology that will be more palatable to our REFERENCES 1. Salem MM: Hypertension in the hemodialysis population: A survey of 649 patients. Am .I Kidney Dis 26:461-468, 1995 2. Raine A, Maryrecker R, Brunner F, Ehrich J, Geerlings W, Laudais P, Loirat C, Mallick N, Selwood N, Tufveson G, Valderrabaus F: Report on management of renal failure in Europe XXII 1991. Nephrol Dial Transplant 2:7-35, 1992 (SUPPU 3. Ritz E, Koch M: Morbidity and mortality due to hypertension in patients with renal failure. Am J Kidney Dis 21:113-118, 1993 (suppl 2) 4. Curtis JR, Eastwood JB, Smith EKM, Storey JM, Verroust PJ, de Wardner HE, Wing AJ, Wolfson EM: Maintenance hemodialysis. Q J Med 38:49-89, 1969 5. Luik AJ, Gladziwa U, Kooman JP, van Houf JP, de Leeuw PW, van Bortel LM, Leunissen KM: Blood pressure changes in relation to interdialytic weight gain. Contrib Nephrol 106:179-185, 1994 6. Tomita J, Kimura G, Inoue T, Irenaga T, Sanai T, Kawano Y, Nakamura S, Baba S, Matsuoka H, Omae T: Role of systolic blood pressure in determining prognosis of hemodialysis patients. Am J Kidney Dis 25:405-412, 1995 7. Vertis V, Cangiano JL, Berman LB: Hypertension in end stage renal disease. N Engl J Med 280:978-981, 1969 8. Wilkinson R, Scott DR, Uldall PR, Kerr DNS, Swinney J: Plasma renin and exchangable sodium in the hypertension of chronic renal failure. Q J Med 39:377-394, 1970 9. Brown JJ, Curtis JR, Lever AF, Robertson JLS, de Wardener HE, Wing AJ: Plasma renin concentration and the control of blood pressure in patients on maintenance hemodialysis. Nephrol 6:329-349, 1969 10. Luik AJ, van Kuijk WHM, Spek J, de Heer F, van Bortel LMAB, Schiffers PMH, van Hooff JP, Leunissen KML: The effects of hypervolemia on interdialytic hemodynamics and blood pressure control in hemodialysis patients. Am J Kidney Dis 30:466-474, 1997 11. Dobbs WA, Prather JW, Guyton AC: Relative importance of nervous control of cardiac output and arterial pressure. Am J Cardiol 27:507-512, 1971 12. Kim KE, Onesti G, de1 Guescio ET, Greco J, Fernandes M, Eidelson B, Swartz C: Sequential hemodynamic changes in end stage renal disease and the anephric state during volume expansion. Hypertension 2:102-110, 1980 13. Katzarski KS, Nisell J, Randmaa I, Danielsson A, Freyschuss U, Bergstrom J: A critical evaluation of ultrasound measurement of inferior vena cava diameter in assessing dry weight in normotensive and hypertensive hemodialysis patients. Am J Kidney Dis 30:459-465, 1997 14. Charra B, Calemand E, Laurent G: Importance of treatment time and blood pressure control in achieving long term survival on dialysis. Am J Nephrol 16:35-44, 1996
H
YPERTENSION is prevalent in patients undergoing chronic dialysis and is likely a significant contributor to the high cardiovascular death rate in the end-stage renal disease (ESRD) population.‘-6 Initial assessments of the mechanisms causing hypertension in the ESRD population concluded that sodium or fluid overload was responsible for elevated blood pressure in 90% of cases, whereas the remaining 10% had elevated plasma renin activities.7-9 Indeed, the concept of using a decrease in blood pressure as the indicator for optimal or dry weight is based on the assumption that elevated blood pressure in hemodialysis patients is primarily the result of sodium or fluid overload. Registry data from Europe showing that 83% of their dialysis population requires blood pressure medications and observations in this country that blood pressure is inadequately controlled in 50% to 85% of presumably adequately dialyzed patients have challenged the dictum that sodium or fluid overload is the seminal mechanism for hypertension in most patients requiring maintenance hemodialysis. This controversy is reflected in the conclusions of two manuscripts published in this issue of the Journal.
Luik et al,” examining the effects of modest changes in vascular volume on interdialytic blood pressure, found no correlation between fluid load or weight gain and interdialytic blood pressure in 10 chronic hemodialysis patients, four of whom had been on antihypertensive therapy before selection for study.” Hypervolemia in this study increased cardiac index and tended to reduce total peripheral resistance index in association with significant reductions in plasma levels of arginine vasopressin and angiotensin II. There was also an increase in atria1 natriuretic factor. The changes reported in these hemodialysis patients are similar to the initial changes observed in experimental animals or humans with normal renal function given a volume challenge. The investigators thus document that the shortand intermediate-term physiological mechanisms essential for buffering direct effects of fluid loads on mean arterial pressure are intact in many hemodialysis patients. Studies examining the relaAmerican
Journal
of Kidney
Diseases,
Vol 30, No 4 (October),
tionship between changes in vascular volume and blood pressure in animals have shown the power of these mechanisms, which when fully operational allow the circulation to absorb up to a 30% increase in blood volume over a period of 4 minutes with minimal change in mean arterial pressure.” Impairment of these mechanisms leads to increased susceptibility to volume-induced hypertension. This observation is reflected in the study by Luik et al, in which hemodialysis patients in whom hypervolemia was associated with increasing interdialytic blood pressure showed less hypervolemia-induced suppression of plasma renin and angiotensin. The findings reported by Luik et al are consistent with earlier observations recorded by Kim et al,‘* who found that sodium and water loading increases blood pressure in chronic hemodialysis patients only in circumstances in which the total peripheral resistance index fails to decrease.” Events that impair ability to reduce total peripheral resistance might include not only failure to suppress renin or angiotensin II, but also abnormal baroreflex sensitivity, increased activation of the sympathetic nervous system, circulating inhibitors of the nitric oxide system, and reduced production or release of prostaglandin and renomedullary lipids. In the presence of such abnormalities, hemodialysis patients may be sensitized to effects of even small increments in vascular volume. An opposite conclusion regarding the role of fluid overload in the development of hypertension in hemodialysis patients was noted in the study reported in this issue of the Journal by Katzarski et a1.13 While evaluating ultrasound measurements of inferior vena cava diameter (IVCD) as a method to assess dry weight in hemodialysis patients, they observed that blood volume correlated with mean arterial pressure both before and after the hemodialysis procedure. Blood volume was higher in hypertensive hemodialysis patients compared with normotensive hemodialysis patients at equivalent body weights both before and after hemodialysis. This observa0 1997 by the National Kidney 0272-6386/97/3004-0022$3.00/O 1997:
pp 577-578
Foundation,
Inc.
577
578
tion suggests that the relationship between plasma volume and weight may be different in hypertensive hemodialysis patients compared with normotensive hemodialysis patients. Measurement of IVCD during or within 2 hours after the dialysis procedure did not increase the accuracy of assessing dry weight. Both IVCD and blood volume increased for several hours after the hemodialysis procedure, presumably as a result of fluid shifts between extravascular and intravascular space. These changes seemed to be more marked in hypertensive hemodialysis patients. The postdialysis increase in IVCD and blood volume could be lessened by increasing dialysis time from 3 to 6 hours, even though postdialysis weights were equivalent in both circumstances. The investigators interpreted their findings as support for the hypothesis that fluid overload plays an important role in the pathogenesis hypertension in hemodialysis patients. Interestingly, mean arterial pressure was not normalized by fluid removal in their hypertensive dialysis patients. Furthermore, if the blood volumes measured in group A patients are representative of their entire study population, their data also suggest that dialysis patients with hypertension remain hypertensive even after their blood volume is reduced to values not different from those found predialysis in normotensives or in healthy subjects. This implies that sodium/fluid overload is not the only factor maintaining elevated blood pressure in the hypertensive hemodialysis patients. Clearly, further investigation will be required to fully elucidate mechanisms contributing to the development and maintenance of hypertension in hemodialysis patients. The available data do not convincingly mandate a change in the approach currently used to manage hypertension in the ESRD population. The impressive blood pressure control and survival data reported from the Centre de Rein Artificiel in Tassin, France, show what is achievable, although their dialysis prescription of three 8-hour sessions per week is, in my experience, unacceptable to most patients receiving hemodialysis in the United States. The challenge for nephrologists in this country is to
KENT
A. KIRCHNER
determine whether similar outcomes can be achieved through other alterations in dialysis technology that will be more palatable to our REFERENCES 1. Salem MM: Hypertension in the hemodialysis population: A survey of 649 patients. Am .I Kidney Dis 26:461-468, 1995 2. Raine A, Maryrecker R, Brunner F, Ehrich J, Geerlings W, Laudais P, Loirat C, Mallick N, Selwood N, Tufveson G, Valderrabaus F: Report on management of renal failure in Europe XXII 1991. Nephrol Dial Transplant 2:7-35, 1992 (SUPPU 3. Ritz E, Koch M: Morbidity and mortality due to hypertension in patients with renal failure. Am J Kidney Dis 21:113-118, 1993 (suppl 2) 4. Curtis JR, Eastwood JB, Smith EKM, Storey JM, Verroust PJ, de Wardner HE, Wing AJ, Wolfson EM: Maintenance hemodialysis. Q J Med 38:49-89, 1969 5. Luik AJ, Gladziwa U, Kooman JP, van Houf JP, de Leeuw PW, van Bortel LM, Leunissen KM: Blood pressure changes in relation to interdialytic weight gain. Contrib Nephrol 106:179-185, 1994 6. Tomita J, Kimura G, Inoue T, Irenaga T, Sanai T, Kawano Y, Nakamura S, Baba S, Matsuoka H, Omae T: Role of systolic blood pressure in determining prognosis of hemodialysis patients. Am J Kidney Dis 25:405-412, 1995 7. Vertis V, Cangiano JL, Berman LB: Hypertension in end stage renal disease. N Engl J Med 280:978-981, 1969 8. Wilkinson R, Scott DR, Uldall PR, Kerr DNS, Swinney J: Plasma renin and exchangable sodium in the hypertension of chronic renal failure. Q J Med 39:377-394, 1970 9. Brown JJ, Curtis JR, Lever AF, Robertson JLS, de Wardener HE, Wing AJ: Plasma renin concentration and the control of blood pressure in patients on maintenance hemodialysis. Nephrol 6:329-349, 1969 10. Luik AJ, van Kuijk WHM, Spek J, de Heer F, van Bortel LMAB, Schiffers PMH, van Hooff JP, Leunissen KML: The effects of hypervolemia on interdialytic hemodynamics and blood pressure control in hemodialysis patients. Am J Kidney Dis 30:466-474, 1997 11. Dobbs WA, Prather JW, Guyton AC: Relative importance of nervous control of cardiac output and arterial pressure. Am J Cardiol 27:507-512, 1971 12. Kim KE, Onesti G, de1 Guescio ET, Greco J, Fernandes M, Eidelson B, Swartz C: Sequential hemodynamic changes in end stage renal disease and the anephric state during volume expansion. Hypertension 2:102-110, 1980 13. Katzarski KS, Nisell J, Randmaa I, Danielsson A, Freyschuss U, Bergstrom J: A critical evaluation of ultrasound measurement of inferior vena cava diameter in assessing dry weight in normotensive and hypertensive hemodialysis patients. Am J Kidney Dis 30:459-465, 1997 14. Charra B, Calemand E, Laurent G: Importance of treatment time and blood pressure control in achieving long term survival on dialysis. Am J Nephrol 16:35-44, 1996