BLOOD PRESSURE CONTROL AND LEFT VENTRICULAR HYPERTROPHY IN LONG- TERM CAPD AND HEMODIALYSIS PATIENTS: A CROSS-SECTIONAL STUDY

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1 Peritoneal Dialysis International, Vol. 23, pp Printed in Canada. All rights reserved /03 $ Copyright 2003 International Society for Peritoneal Dialysis BLOOD PRESSURE CONTROL AND LEFT VENTRICULAR HYPERTROPHY IN LONG- TERM CAPD AND HEMODIALYSIS PATIENTS: A CROSS-SECTIONAL STUDY Ali Ihsan Günal, 1 Erdogan Ilkay, 2 Ercan Kirciman, 1 Ilgin Karaca, 2 Ayhan Dogukan, 1 and Huseyin Celiker 1 Departments of Nephrology 1 and Cardiology, 2 Firat University Medical School, Elazig, Turkey Background: It is still not clear whether hypertension and left ventricular hypertrophy (LVH) are more common in continuous ambulatory peritoneal dialysis (CAPD) than in hemodialysis (HD) patients. Methods: To examine this subject, the indices of cardiac performance were compared between 50 HD and 34 CAPD patients. Patients were further divided into two subgroups [long-term (L) CAPD and L-HD] according to dialysis modality and duration of dialysis (more than 60 months duration). Results: The blood pressure and cardiothoracic index of CAPD patients did not differ from HD patients. On average, the left atrial index was 2 mm/m 2 higher in HD patients than in CAPD patients. Left ventricular chamber sizes, wall thickness, and left ventricular mass index (LVMI) in patients on CAPD were similar to those of HD patients. Isovolumic relaxation time (IVRT) of CAPD patients was insignificantly less than that of HD patients (101 ± 22 and 115 ± 27 msec respectively). There was no significant difference between the two subgroups (L-HD and L-CAPD) in blood pressure, left atrial diameter, left ventricular chamber size, wall thickness, LVMI, ejection fraction, or IVRT. Conclusion: If normovolemia and normotension are obtained by strict volume control without using antihypertensive drugs, the effects of the two modalities of chronic dialysis treatment (HD and CAPD) on cardiac structure and function are not different from each other. Perit Dial Int 2003; 23: KEY WORDS: Hemodialysis; left ventricular hypertrophy; echocardiography; strict volume control. Cardiovascular disease has been reported to be the main cause of death in patients on chronic dialysis. It has been shown that survival of patients on continuous ambulatory peritoneal dialysis (CAPD) is similar to that of hemodialysis (HD) patients (1). It has been accepted that volume overload is the main Correspondence to: A.I. Günal, Firat Üniversitesi Tip Fakültesi, Nefroloji Bilim Dali, 23200, Elazig, Turkey. igunal@yahoo.com Received 21 February 2003; accepted 28 May cause of hypertension in patients on chronic dialysis (2,3). Hypertension is a major risk factor for cardiac diseases, including left ventricular hypertrophy (LVH), left ventricular dilatation, heart failure, and ischemic heart disease. Among these, LVH was associated with significantly high cardiovascular morbidity and mortality in chronic CAPD patients, similar to HD patients (4,5). Controlling fluid and salt balances is the major issue in dialysis patients and particularly in CAPD patients with minimal or no residual renal function. Because CAPD makes it possible to remove large amounts of fluid more gradually, control of hypertension should be easier in these patients. Early reports showed that CAPD provided more effective control of volume overload and hypertension (6,7); however, recent studies examining whether there are any differences in the long-term effects of dialysis modalities on cardiac performance seem to indicate the contrary (8,9). According to these reports, the proportion of patients with hypertension and/or LVH, the use of antihypertensive drugs, and cardiovascular events increased and equaled or even exceeded those of HD patients. In this study, we present a cross-sectional analysis of blood pressure control and cardiac performance in chronic dialysis patients by using echocardiography and pulsed Doppler echocardiography. The results were compared between HD and CAPD patients and patients with long-term duration of either dialysis modality. MATERIALS AND METHODS We apply strict volume control in our dialysis center. When the (mostly ineffective) antihypertensive drugs are discontinued, the need for salt restriction is re-emphasized, explaining to patients and their families the meaning of a salt-restricted diet and avoidance of ready-made food. As this approach is often not sufficient, repeated instructions are given to change patients attitudes. After this approach, we 563

2 GÜNAL et al. NOVEMBER 2003 VOL. 23, NO. 6 PDI estimated salt intake by dietary analysis to be around 4 5 g/day. Patients are allowed to drink as much as their thirst indicates, as long as salt is restricted. At the time of data collection, 56 and 38 patients attended our HD and CAPD programs respectively. Six HD and 4 CAPD patients that had intercurrent acute illness, valvular heart disease, cardiac arrhythmia or conduction defect, regional wall motion abnormalities, or technically uninterpretable two-dimensional echocardiogram were not enrolled in the study. The remaining 84 patients (50 HD and 34 CAPD) were enrolled in the study after their informed consents were obtained. At the time of the study, 2 of the 4 hypertensive CAPD patients had residual urine production more than 500 ml/day; the remaining 82 patients had no residual renal function. None of the patients were using diuretic or antihypertensive drugs. Ten of the 50 (20%) HD and 8 of 34 (24%) CAPD patients were diabetic. HEMODIALYSIS PATIENTS Fifty HD patients were subjected to the study. The female/male ratio of the group was 28/22 and their mean age was 49 ± 15 years (range years). The duration of dialysis ranged from 4 to 205 months (mean 45 ± 43 months). Their interdialytic weight gain was 1.9 ± 0.8 kg. Hemodialysis was performed for 4 5 hours three times weekly. When their interdialytic weight gain was too much, an extra ultrafiltration session was added at the end of HD. In this way, no patient remained hypertensive at the end of an HD session. Bicarbonate dialysis fluid containing 136 mmol/l Na and 3 meq/l Ca was used. A polysulfone dialyzer, m 2 surface area (Fresenius Medical Care, Bad Homburg, Germany) was used. Blood flow was ml/minute; dialysate flow was 500 ml/minute. Ultrafiltration was controlled volumetrically in all HD machines used in this study (Table 1). CAPD PATIENTS The CAPD group was composed of 34 patients. The female/male ratio of the group was 12/22 and their mean age was 45 ± 16 years (range years). The duration of dialysis ranged from 4 to 90 months (mean 33 ± 27 months). CAPD was performed by patients using L glucose dialysate (Na 132 mmol/l, lactate 35 mmol/l, Ca 1.25 mmol/l) per exchange for 4 5 exchanges daily. If necessary, continuous cyclic peritoneal dialysis was performed with L dialysate for 8 10 exchanges daily (8 patients). At the start of this study, one bag was an icodextrin (7.5 g/dl) solution in 25 patients for 2 years (Table 1). 564 TABLE 1 Main Clinical and Laboratory Data of the Patients LONG-TERM EFFECT OF DIALYSIS TREATMENT ON CARDIAC PERFORMANCE To test the effect of long-term dialysis treatment on the indices of cardiac performance, the patients were subdivided into two groups according to dialysis duration: long-term HD (L-HD), composed of 17 of 50 HD patients, on HD for more than 60 months (age 47 ± 14 years, HD duration 89 ± 39 months); and longterm CAPD (L-CAPD), composed of 9 of 34 CAPD patients, on CAPD for more than 60 months (age 41 ± 10 years, CAPD duration 72 ± 10 months). None of the long-term patients were diabetic. BLOOD PRESSURE MEASUREMENT Hypertension was defined according to WHO/ISH criteria (presence of one of the following criteria: systolic blood pressure > 140 mmhg, diastolic blood pressure > 90 mmhg). Blood pressure was measured with a manual sphygmomanometer. In CAPD patients, blood pressure values are given as the mean of 3 measurements after 5-minute resting periods. In HD patients, the blood pressures given in this article are the mean of at least 3 consecutive predialysis recordings. ECHOCARDIOGRAPHY HD (n=50) CAPD (n=34) p Value Females/Males 28/22 12/22 NS Age (years) 49±15 45±16 NS Duration of dialysis (months) 45±43 33± Serum albumin (g/dl) 3.8± ±0.4 NS Calcium phosphate 45±12 44±15 NS Hemoglobin (g/dl) 11±1.7 12±2.3 NS On rhuepo 7 (14%) 2 (5%) NS Kt/V 1.3± ±0.2 (Weekly) Diabetic patients 10 (20%) 8 (24%) NS Hypertensive patients 5 (10%) 4 (11%) NS Interdialytic weight gain (kg) 1.9±0.8 Ultrafiltration volume (ml) 1192±297 HD = hemodialysis; CAPD = continuous ambulatory peritoneal dialysis; NS = not significant; rhuepo = recombinant human erythropoietin. Echocardiographic examination was performed using an ATL-Ultramark 9 ultrasonoscope with 2.5-MHz transducer (Advanced Technology Laboratories, Bothell, Washington, USA), according to the recommendations of the American Society of Echo-

3 PDI NOVEMBER 2003 VOL. 23, NO. 6 CARDIAC PERFORMANCE AND LONG-TERM CAPD cardiography (10). An experienced echocardiographer who was blinded to the study design made all the measurements. The values of each parameter were averaged over three cardiac cycles. Echocardiographic examination was performed the day after dialysis in HD patients and with an empty abdomen in CAPD patients. The left ventricular mass index (LVMI) was calculated using the following equation: LVMI (g/m 2 ) = 1.04 [(IVST + LVDD + PWT) 3 (LVDD) 3 ] /body surface area, where IVST = interventricular septum thickness; LVDD = left ventricular end-diastolic diameter; and PWT = posterior wall thickness. Left ventricular systolic function was assessed by the left ventricular ejection fraction. Peak flow velocities of the early (E) and late (A) diastolic fillings, their ratio (E/A), and isovolumic relaxation time (IVRT) were used in the assessment of left ventricular diastolic performance. STATISTICAL ANALYSIS All data are expressed as mean ± SD. Comparisons between groups were made by t-test or by Mann Whitney test, as appropriate. If the group variances were not homogeneous as evidenced by Levene s test, p values were adjusted. The power analyses of these tests were performed by G-power, a general power analysis program. Differences in proportions were tested by chi-square test. Stepwise multiple regression analysis was performed to define the predictors of LVMI. A p value less than 0.05 was considered significant. RESULTS The CAPD patients had been treated for a shorter time than the HD patients. There was no difference between the two groups (HD and CAPD) in female/ male ratio, age, the level of serum albumin, calcium phosphate product, hemoglobin, erythropoietin use, or the number of hypertensive and diabetic patients (Table 1). Blood pressure and cardiothoracic index in CAPD patients did not differ from HD patients. On average, left atrial index was 2 mm/m 2 higher in HD than in CAPD patients. Left ventricular chamber sizes, wall thickness, and LVMI in patients on CAPD were similar to those of HD patients. The E/A ratio in CAPD patients was comparable to that in HD patients. The IVRT was insignificantly less in CAPD patients than in HD patients (101 ± 22 and 115 ± 27 msec respectively). Systolic function, evidenced by ejection fraction of the left ventricle, in CAPD patients was the same as that in HD patients (Table 2). The power of t-test was 85%. Blood pressure in L-CAPD patients was similar to that in L-HD patients. There was no significant difference between the two groups (L-HD and L-CAPD) in left atrial diameter and left ventricular chamber sizes, wall thickness, LVMI, IVRT, or ejection fraction (Table 3). The power of Mann Whitney test was 92%. The LVMI correlated positively with age (r = 0.37, p = 0.002), systolic blood pressure (r = 0.27, p = 0.027), diastolic blood pressure (r = 0.25, p = 0.04), and left atrial index (r = 0.59, p = ), and inversely with hemoglobin (r = 0.28, p = 0.021) and serum albumin (r = 0.29, p = 0.017). Modality of treatment (p = 0.21), duration of dialysis treatment (p = 0.84), calcium phosphate (p = 0.65), and diabetes (p = 0.15) did not correlate with LVMI. To define the independent determinants of LVMI, we modeled a multivariate analysis. Left atrial index, systolic and diastolic blood pressure, and age were found to be independent predictors of LVMI (p < ) (Table 4). DISCUSSION This study provides important evidence that the effects of the modalities of chronic dialysis treatment TABLE 2 Blood Pressure and Echocardiographic Parameters of the Patients HD CAPD (n=50) (n=34) p Value Systolic pressure (mmhg) 115±23 122±17 NS Diastolic pressure (mmhg) 74±14 76±12 NS Cardiothoracic ratio (%) 46±4 46±5 NS Left atrial index (mm/m 2 ) 22±3 20±2 NS LVESDI (mm/m 2 ) 18±3 17±2 NS LVEDDI (mm/m 2 ) 28±5 26±3 NS IVST (mm) 12.5±2 11.8±2 NS PWT (mm) 11.5±2 11±1.6 NS LVMI (g/m 2 ) 119±35 113±37 NS LVH (Korean criteria) 10 (20%) 6 (17%) NS E/A 0.86± ±0.3 NS IVRT (msec) 115±27 101±22 NS Ejection fraction (%) 63±8 63±7 NS HD = hemodialysis; CAPD = continuous ambulatory peritoneal dialysis; NS = not significant; LVESDI = left ventricular end-systolic diameter index; LVEDDI = left ventricular end-diastolic diameter index; IVST = interventricular septum thickness; PWT = posterior wall thickness; LVMI = left ventricular mass index (<125 g/m 2 ); E = peak early diastolic mitral velocity (cm/sec); A = peak late diastolic mitral velocity (cm/sec); IVRT = isovolumic relaxation time (mean 83±16 msec). 565

4 GÜNAL et al. NOVEMBER 2003 VOL. 23, NO. 6 PDI TABLE 3 Blood Pressure and Echocardiographic Data in Long- Term Hemodialysis (L-HD) and Long-Term Continuous Ambulatory Peritoneal Dialysis (L-CAPD) Patients (HD and CAPD) on cardiac structure and function are not different from each other, if normovolemia and normotension are obtained by strict volume control without using antihypertensive drugs. Our findings are contrary to recent studies that suggest CAPD patients with a long duration of treatment are more volume-expanded than HD patients, and that they may have higher blood pressure and more severe LVH (8,9). Theoretically, because dietary salt and water can be removed continuously and not intermittently as in HD, it should be much easier to control body water volume with CAPD. Early studies 566 L-HD L-CAPD (n=17) (n=9) p Value Age (years) 47±14 41±10 NS Duration of dialysis (months) 89±39 72± Ultrafiltration volume (ml) 1136±180 Interdialytic weight gain (kg) 1.8±0.4 Cardiothoracic ratio (%) 48±3 46±3 NS Systolic pressure (mmhg) 111±23 111±20 NS Diastolic pressure (mmhg) 70±16 75±11 NS Left atrial index (mm/m 2 ) 22±4 19±2 NS LVESDI (mm/m 2 ) 19±2 17±2 NS LVEDDI (mm/m 2 ) 27±4 26±3 NS IVST (mm) 12±1.3 11±1.9 NS PWT (mm) 11±1.7 10±1.9 NS LVMI (g/m 2 ) 112±27 102±27 NS E/A 0.92± ±0.3 NS IVRT (msec) 114±19 88±17 NS Ejection fraction (%) 62±7 66±3 NS NS = not significant; LVESDI = left ventricular end-systolic diameter index; LVEDDI = left ventricular end-diastolic diameter index; IVST = interventricular septum thickness; PWT = posterior wall thickness; LVMI = left ventricular mass index (<125 g/m 2 ); E = peak early diastolic mitral velocity (cm/sec); A = peak late diastolic mitral velocity (cm/sec); IVRT = isovolumic relaxation time (mean 83±16 msec). TABLE 4 Multiple Regression of Left Ventricular Mass Index Independent variables Beta p Value Left atrial index (mm/m 2 ) Systolic blood pressure (mmhg) Age (years) Diastolic blood pressure (mmhg) Multiple r = 0.59; p < suggested that CAPD allows better extracellular volume and blood pressure control, confirming our results (6,7). However, after years of CAPD, the proportion of patients with hypertension, the number of hypotensive drugs given (and consequently the proportion of patients with LVH), and the number of cardiovascular events increased and equaled or even surpassed those of HD patients (8,9,11). There may be several reasons why volume control and, as a result, blood pressure control and cardiac events, may gradually become deranged with time on CAPD. First, the majority of patients are admitted to CAPD while they still have considerable residual renal function, contributing significant volume control. With time on CAPD, residual renal function disappears and it becomes hard to control body fluid volume. If hypertension in CAPD patients is treated by strict volume control, residual renal function is rapidly lost (3,12). Another reason for deranged volume control is the loss of ultrafiltration capacity of the peritoneal membrane. At the beginning of CAPD treatment, good ultrafiltration efficacy and residual renal function make volume control easy and salt restriction non-obligatory. A recent study suggested that patients on CAPD should consume at least 200 mmol/day sodium (13). In such a condition, we decrease the use of hypertonic glucose solutions instead of increasing dietary salt intake. In addition, if patients are permitted to consume a large amount of salt at the beginning, later it is difficult to convince them that salt is bad for them. After all, with time on CAPD, to obtain normovolemia and normal blood pressure, the use of hypertonic peritoneal dialysis solution increases. Consequently, the increased use of hypertonic glucose solution may accelerate the loss of ultrafiltration capacity of the peritoneal membrane (14,15). The third reason for impaired volume control is that these patients are seen by a doctor or nurse much less frequently than are HD patients, which also complicates good volume control. One of the reasons why we obtained good volume control in our center is that every patient on CAPD measures blood pressure and body weight at home. If a patient notices an increase in blood pressure or body weight, he or she comes to the center as soon as possible. Then, we evaluate the patient s dietary compliance and possible catheter malposition. First, if there is no problem with the catheter, salt restriction is re-emphasized. One week later, the patient is admitted to the clinic. If normal blood pressure and normovolemia (evidenced by cardiothoracic index < 0.48) cannot be obtained by salt restriction alone, ultrafiltration is adjusted by instructing the patient to use hypertonic dextrose solution to decrease their weight. Thereafter it is often possible to decrease or abolish the two conditions, depending upon the patient s condition.

5 PDI NOVEMBER 2003 VOL. 23, NO. 6 CARDIAC PERFORMANCE AND LONG-TERM CAPD Although our results are intriguing, one should consider the limitations of this study. Apart from the cross-sectional design, which precludes assessment of time-dependent changes in the present study, another important limitation deserves attention. The number of patients studied was relatively small, which does not permit a firm conclusion about differences among the groups. Also, we cannot exclude the possibility that some of the differences between our CAPD and HD patients were present at initiation of dialysis. However, the number of patients is too small to allow comprehensive covariate adjustment. In conclusion, our study shows that there is no difference between the two chronic dialysis modalities in long-term control of blood pressure and cardiac structure and function if extracellular fluid volume is strictly controlled. REFERENCES 1. Vonesh EF, Moran J. Mortality in end-stage renal disease: a reassessment of differences between patients treated with hemodialysis and peritoneal dialysis. J Am Soc Nephrol 1999; 10: Hegstrom RM, Murray JS, Pendras JP, Burnell JM, Scribner BH. Hemodialysis in the treatment of chronic uremia. ASAIO Trans 1961; 7: Gunal AI, Duman S, Ozkahya M, Toz H, Asci G, Akcicek F, et al. Strict volume control normalizes hypertension in peritoneal dialysis patients. Am J Kidney Dis 2001; 37: Silaruks S, Sirivongs D, Chunlertrith D. Left ventricular hypertrophy and clinical outcome in CAPD patients. Perit Dial Int 2000; 20: Ohashi H, Oda H, Ohno M, Sakata S. Predictors of survival in continuous ambulatory peritoneal dialysis patients: the importance of left ventricular hypertrophy and diabetic nephropathy. Adv Perit Dial 1999; 15: Saldanha LF, Elmar WJ, Weiler WJ, Gonick HC. Effect of continuous ambulatory peritoneal dialysis on blood pressure. Am J Kidney Dis 1993; 21: Cannata JB, Isles CG, Briggs JD, Junor BJR. Comparison of blood pressure control during hemodialysis and CAPD. Dialysis & Transplantation 1986; 15: Enia G, Mallamaci F, Benedetto FA, Panuccio V, Parlongo S, Cutrupi S, et al. Long-term CAPD patients are volume expanded and display more severe left ventricular hypertrophy than haemodialysis patients. Nephrol Dial Transplant 2001; 16: Takeda K, Nakamoto M, Hirakata H, Baba M, Kubo M, Fujishima M. Disadvantage of long-term CAPD for preserving cardiac performance: an echocardiographic study. Am J Kidney Dis 1998; 32: Sahn DJ, DeMaria A, Kisslo J. Recommendations regarding quantification in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978; 58: Lameire N. The impact of residual renal function on the adequacy of peritoneal dialysis. Nephron 1997; 77: Hufnagel G, Michel C, Queffeulou G, Skhiri H, Damieri H, Mignon F. The influence of automated peritoneal dialysis on the decrease in residual renal function. Nephrol Dial Transplant 1999; 14: Fine A, Fontaine B, Ma M. Commonly prescribed salt intake in continuous ambulatory peritoneal dialysis patients is too restrictive: results of a double-blind crossover study. J Am Soc Nephrol 1997; 8: Gunal AI, Celiker H, Akpolat N, Ustundag B, Duman S, Akcicek F. By reducing production of vascular endothelial growth factor octreotide improves the peritoneal vascular alterations induced by hypertonic peritoneal dialysis solution. Perit Dial Int 2002; 22: Gunal AI, Duman S, Sen S, Unsal A, Terzioglu E, Akcicek F, et al. By reducing TGF beta 1, octreotide lessens the peritoneal derangement induced by a high glucose solution. J Nephrol 2001; 14: