IJCA-18041; No of Pages 3 International Journal of Cardiology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the editor
Risk of intradialytic hypotension in patients on thrice-weekly versus twice-weekly hemodialysis Guangtao Lei a,1, Xia Li b,1, Weiping Tu c, Chengyun Xu c, Zibing Duan c, Xianfeng Wu c,⁎ a b c
Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang, China Department of Nephrology, the First People Hospital of Jining, Jining, China Department of Nephrology, the Second Affiliated Hospital of Nanchang University, Nanchang, China
a r t i c l e
i n f o
Article history: Received 7 April 2014 Accepted 12 April 2014 Available online xxxx Keywords: Intradialytic hypotension Thrice-weekly hemodialysis Risk Twice-weekly hemodialysis
Being afraid of inadequate dialysis, thrice-weekly HD has been regarded as a standard renal replacement therapy (RRT) for ESRD patients [1]. Nevertheless, twice-weekly HD remains prevalent in the developing countries and also could be found in some developed countries [2,3]. Thus far, scarce data are available for the clinical outcomes, especially intradialytic hypotension (IDH), of twice-weekly HD patients. Few studies have used a rigorous definition of IDH according to the European Best Practice Guidelines (EBPG), which defines as both a fall blood pressure and the occurrence of symptoms requiring an intervention [4]. IDH is the most commonly adverse effect of HD [5,6] and is strongly associated with many adverse clinical events [7–9]. A previous study reported that patients on twice-weekly HD suffered from significantly fewer IDH episodes compared with those thrice-weekly HD [10]. Nonetheless, the definition of IDH was markedly different from that of EBPG, which may contribute to bias of their findings. Furthermore, the risk of IDH failed to be evaluated in patients undergoing thrice-weekly HD as compared with those with twice-weekly HD in that study. Therefore, the purpose of this work was to evaluate the risk of IDH in patients on thrice-weekly vs. twice-weekly HD.
⁎ Corresponding author at: Department of Nephrology, the Second Affiliated Hospital of Nanchang University, Minde Road I, Donghu District, Nanchang, Jiangxi Province, China, 330006. Tel.: +86 791 86312551. E-mail address: [email protected] (X. Wu). 1 Contributed equally to this study.
From January 1, 2013, to December 31, 2013, 129 incident and prevalent patients were recruited from a single HD center of the Second Affiliated Hospital of Nanchang University. Enrollment included patients aged ≥18 years who had received HD for N3 months, except those who had undergone peritoneal dialysis (PD) previously, malignant disease or refused to give written consent. This work was a prospective study. Eligible patients were divided into two groups according to nephrologists' recommendation and patients' choice: twice-weekly group and thrice-weekly group. Baseline characteristics, including age, sex, HD vintage, dry weight, urine output, diabetes, pre-existing cardiovascular disease (CVD), hypertension as well as etiology of renal disease were collected at the initiation of entry of this study. Time-dependent parameters included hemoglobin, hematocrit, uric acid, calcium phosphate product, intact parathormone (iPTH), ferritin, albumin, cholesterol and spKt/v (spKt/v). The primary outcome was IDH. Patients were followed up until death, transfer to PD therapy, kidney transplantation, transfer of care from our center or censoring on December 31, 2013. The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University. All patients provided informed consent before study entry. Diagram flow was show in Fig. 1. In our study, 93 (72.1%) were in the twice-weekly group and 36 (27.9%) in the thrice-weekly group. Compared with patients on twice-weekly HD, thrice-weekly HD patients had significantly lower urine output (p b 0.001) but higher calcium phosphate product (p b 0.001, Table 1). During the follow-up, 12 (12.9%) patients developed IDH in the twice-weekly group and 10 (27.8%) in the thrice-weekly group. IDH incidence was significantly higher in the thrice-weekly group as compared to the twice-weekly group [odds ratios 2.60, 95% confidence index (CI) 1.13–3.85, p = 0.044]. Multivariate analysis showed that older age [hazard ratio (HR) 1.03, 95% CI = 1.01–1.07, p = 0.048], higher calcium phosphate product (HR = 1.04, 95% CI = 1.01–1.07, p = 0.042), and thrice-weekly HD (with twice-weekly HD as reference, HR = 2.63, 95% CI = 1.13–3.89, p = 0.047) were independently associated with increased the risk of IDH in this study population (Table 2). On multivariate analysis, older age (HR = 1.02, 95% CI = 1.01–1.07, p = 0.028) and higher calcium phosphate product (HR = 1.10, 95% CI = 1.03–1.18, p = 0.009) were independently risk factors for IDH in thrice-weekly HD patients (Table 3). Table 4 showed that older age (HR = 1.03, 95% CI = 1.01–
http://dx.doi.org/10.1016/j.ijcard.2014.04.140 0167-5273/© 2014 Elsevier Ireland. Ltd. All rights reserved.
Please cite this article as: Lei G, et al, Risk of intradialytic hypotension in patients on thrice-weekly versus twice-weekly hemodialysis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.140
2
G. Lei et al. / International Journal of Cardiology xxx (2014) xxx–xxx
Fig. 1. Flow diagram. PD, peritoneal dialysis; HD,hemodialysis; IDH, intradialytic hypotension.
1.13, p = 0.041), pre-existing CVD (HR = 1.84, 95% CI = 1.06–3.34, p = 0.035) and higher calcium phosphate product (HR = 1.09, 95% CI = 1.03–1.17, p = 0.037) were independently predictors for IDH in those on twice-weekly HD. Fig. 2 showed that a significant difference between IDH and their association with HD frequency was observed, with higher cumulative IDH in patients on thrice-weekly HD (log rank = 13.458, p = 0.005). Patients with thrice-weekly HD had significantly higher IDH incidence than those with twice-weekly HD (HR = 2.47, 95% CI = 1.19–3.69, p = 0.044), when extensive demographics, comorbidities and lab adjustments were made (Table 5). A previous study has reported that patients undergoing twiceweekly HD had fewer IDH episodes compared to those undergoing thrice-weekly HD [10]. However, in that study, the definition of IDH was remarkably different from that defined by the EBPG. Thus, the
Table 2 Hazard ratio of IDH in multivariate Cox regression analysis of all HD patientsa. Total patients (n = 129)
Age (per 1 year increase) Urine output (per 100 mL increase) Diabetes (yes/no) Calcium phosphate productb Albumin (per 1 g/L increase) Thrice-weekly HDc
HR
95% CI
p value
1.03 1.00 1.82 1.04 0.92 2.63
1.01–1.07 0.98–1.01 0.65–5.09 1.01–1.07 0.82–1.02 1.13–3.89
0.048 0.530 0.253 0.042 0.103 0.047
a
Factors, which had a difference in relative risk of events by N 10% (b0.90 or N1.1) in the univariate analysis, were included in the multivariate analysis [13].bPer 10 increase.cReference group was twice-weekly HD. IDH = intradialytic hypotension; HD = hemodialysis; HR = hazard ratio; CI = confidence index.
Table 1 Baseline data of total HD patients.
Age (years) Male (%) HD vintage (months) Dry weight (kg) Urine output (mL/24 h) Diabetes (%) Pre-existing CVD (%) Hypertension (%) Etiology of renal disease (%) Chronic glomerulonephritis (%) Diabetic nephropathy (%) Hypertensive nephrosclerosis (%) Other/unknown (%) Lab measurements Hemoglobin (g/L) Hematocrit (%) Serum uric acid (μmol/L) Calcium phosphate product iPTH (pg/mL) Ferritin (ng/mL) Albumin (g/L) Cholesterol (mmol/L) spKt/v
Total patients (n = 129)
Twice-weekly group (n = 93)
Thrice-weekly group (n = 36)
p value
61.8 ± 14.9 86 (66.7) 12.3(8.4–25.0) 57.8 ± 10.3 400.0(0.0–800.0) 45 (34.9) 29 (22.5) 112(86.8)
61.4 ± 15.9 63 (66.7) 11.4(7.9–22.0) 57.9 ± 9.5 500.0(200.0–1000.0) 29(31.2) 22 (23.7) 78(83.9)
62.9 ± 12.9 23 (63.9) 17.1(10.3–27.3) 57.7 ± 12.4 100.0(0.0–200.0) 16 (44.4) 7 (19.4) 34(94.4)
0.599 0.677 0.072 0.946 b0.001 0.125 0.607 0.111
47 (36.4) 42(32.6) 22(17.1) 18(14.0)
38 (40.9) 25(26.9) 18(19.4) 12(12.9)
11 (25.0) 17(47.2) 4(11.1) 6(16.7)
0.093 0.027 0.264 0.580
90.9 ± 18.3 27.8 ± 11.4 442.7 ± 100.6 47.4 ± 14.3 199.4(124.9–359.4) 247.7(170.6–345.3) 35.8 ± 4.3 3.9 ± 1.0 1.3 ± 0.3
89.4 ± 18.9 27.9 ± 13.1 447.4 ± 112.0 44.1 ± 11.2 175.4(123.4–347.0) 254.4(168.4–344.8) 35.9 ± 4.0 3.9 ± 0.9 1.2 ± 0.3
91.5 ± 11.6 27.4 ± 4.9 430.5 ± 62.0 55.7 ± 15.9 232.5(134.3–407.4) 218.3(174.6–346.5) 35.6 ± 5.0 4.0 ± 1.1 1.3 ± 0.3
0.552 0.870 0.392 b0.001 0.191 0.594 0.793 0.703 0.209
HD, hemodialysis; CVD, cardiovascular disease; iPTH, intact parathormone; spKt/v, single pool Kt/v.
Please cite this article as: Lei G, et al, Risk of intradialytic hypotension in patients on thrice-weekly versus twice-weekly hemodialysis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.140
G. Lei et al. / International Journal of Cardiology xxx (2014) xxx–xxx
3
Table 3 Hazard ratio of IDH in multivariate Cox regression analysis of patients on thrice-weekly HDa. Thrice-weekly group (n = 36)
Age (per 1 year increase) HD vintage (per 1 month increase) Diabetes (yes/no) Pre-existing CVD (yes/no) Calcium phosphate productb
HR
95% CI
p value
1.02 1.01 1.82 1.35 1.10
1.01–1.07 0.99–1.04 0.73–5.31 0.99–3.46 1.03–1.18
0.028 0.235 0.182 0.149 0.009
a Factors, which had a difference in relative risk of events by N 10% (b0.90 or N1.1) in the univariate analysis, were included in the multivariate analysis [13].bPer 10 increase. IDH, intradialytic hypotension; HD, hemodialysis; CVD, cardiovascular disease; HR, hazard ratio; CI, confidence index.
Table 4 Hazard ratio of IDH in multivariate Cox regression analysis of patients on twice-weekly HDa.
Fig. 2. Crude analysis of IDH between twice-weekly HD and thrice-weekly HD (Kaplan– Meier estimates of IDH). IDH, intradialytic hypotension; HD, hemodialysis.
Twice-weekly group (n = 93)
Age (per 1 year increase) Pre-existing CVD (yes/no) Hemoglobin (per 1 g/L increase) Hematocrit (per 1% increase) Calcium phosphate product b Serum ferritin (per 1 ng/mL increase) spKt/v (per 0.1 increase)
HR
95% CI
p value
1.06 1.84 1.02 0.91 1.09 1.00 0.83
1.01–1.13 1.06–3.34 0.90–1.14 0.81–1.03 1.03–1.17 0.99–1.01 0.59–2.13
0.041 0.035 0.771 0.128 0.037 0.218 0.336
a Factors, which had a difference in relative risk of events by N 10% (b0.90 or N1.1) in the univariate analysis, were included in the multivariate analysis [13].bPer 10 increase. IDH, intradialytic hypotension; HD, hemodialysis; CVD, cardiovascular disease; spKt/v, single pool Kt/v; HR, hazard ratio; CI, confidence index.
disparity of IDH definition may contribute to bias of that study findings. In addition, the risk of IDH in that study failed to be investigated in patients with thrice-weekly HD compared with those twice-weekly HD. In our study, patients on thrice-weekly HD had higher IDH hazard (HR = 2.47) than those with twice-weekly HD. One of causes of the results may be: HD per se is not a physiological treatment and is associated with unstable cardiovascular homeostasis [11]. Compared to thrice-weekly HD, a twice-weekly HD has less weekly unstable cardiovascular homeostasis because of the lower frequency of HD, which may potentially benefit the twice-weekly HD. Nonetheless, the underlying mechanisms connecting IDH with HD frequency are still far from being well understood. In our study, pre-existing CVD conveys a higher independent risk of IDH in those undergoing twice-weekly HD (HR = 1.84). Additionally, previous study reported that increasing of calcium concentration in
Table 5 Risk of IDH in thrice-weekly vs. twice-weekly HD. Thrice-weekly group (n = 36)
Unadjusted Model 1 Model 2 Model 3
HR
95% CI
p value
2.61 2.63 2.49 2.47
1.11–3.72 1.14–3.89 1.21–3.91 1.19–3.69
0.049 0.032 0.039 0.044
Note: Reference group is twice-weekly HD (n = 93). Model 1: adjusted for age, sex, dry weight and urine output. Model 2: adjusted for model 1 covariates and diabetes, pre-existing CVD and hypertension. Model 3: adjusted for model 2 covariates and hemoglobin, hematocrit, serum uric acid, calcium phosphate product, iPTH, ferritin, albumin, cholesterol and Kt/v. IDH, intradialytic hypotension; HD, hemodialysis; CVD, cardiovascular disease; iPTH, intact parathormone; spKt/v, single pool Kt/v; HR, hazard ratio; CI, confidence index.
dialysate may protect against IDH in some patients [12]. Results in our study showed that higher calcium phosphate product, as a potentially modifiable treatment-related parameter, was independently associated with increased risk of IDH in HD patients, regardless of HD frequency. Three limitations were noted. First, this was a prospective singlecenter study with a small number of participants and limited followup. Second, we failed to analyze weekly Kt/v in this study. Lastly, patients failed to be randomly assigned into thrice-weekly HD or twice-weekly HD. In conclusion, patients on thrice-weekly HD may be associated with increased risk of IDH as compared to those with twice-weekly HD. Given the global epidemic of ESRD and the escalating financial burden of RRT, our findings have important clinical implications. Acknowledgements We thank all staffs in our HD center to make contribution for data collection, excellent patients care, and so on. References [1] Clinical practice guidelines for hemodialysis adequacy, update 2006. Am J Kidney Dis 2006;48(Suppl. 1):S2–S90. [2] Couchoud C, Kooman J, Finne P, et al. From registry data collection to international comparisons: examples of haemodialysis duration and frequency. Nephrol Dial Transplant 2009;24:217–24. [3] Hanson JA, Hulbert-Shearon TE, Ojo AO, et al. Prescription of twice-weekly hemodialysis in the USA. Am J Nephrol 1999;19:625–33. [4] Kooman J, Basci A, Pizzarelli F, et al. EBPG guideline on haemodynamic instability. Nephrol Dial Transplant 2007;22(Suppl. 2):ii22–44. [5] Davenport A. Intradialytic complications during hemodialysis. Hemodial Int 2006;10:162–7. [6] Davenport A, Cox C, Thuraisingham R. Achieving blood pressure targets during dialysis improves control but increases intradialytic hypotension. Kidney Int 2008;73:759–64. [7] Owen PJ, Priestman WS, Sigrist MK, et al. Myocardial contractile function and intradialytic hypotension. Hemodial Int 2009;13:293–300. [8] Mizumasa T, Hirakata H, Yoshimitsu T, et al. Dialysis-related hypotension as a cause of progressive frontal lobe atrophy in chronic hemodialysis patients: a 3-year prospective study. Nephron Clin Pract 2004;97:c23–30. [9] Shoji T, Tsubakihara Y, Fujii M, Imai E. Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients. Kidney Int 2004;66:1212–20. [10] Lin YF, Huang JW, Wu MS, et al. Comparison of residual renal function in patients undergoing twice-weekly versus three-times-weekly haemodialysis. Nephrology (Carlton) 2009;14:59–64. [11] Lin X, Yan Y, Ni Z, et al. Clinical outcome of twice-weekly hemodialysis patients in shanghai. Blood Purif 2012;33:66–72. [12] Maynard JC, Cruz C, Kleerekoper M, Levin NW. Blood pressure response to changes in serum ionized calcium during hemodialysis. Ann Intern Med 1986;104:358–61. [13] Trivedi H, Xiang Q, Klein JP, et al. Risk factors for non-fatal myocardial infarction and cardiac death in incident dialysis patients. Nephrol Dial Transplant 2009;24:258–66.
Please cite this article as: Lei G, et al, Risk of intradialytic hypotension in patients on thrice-weekly versus twice-weekly hemodialysis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.140
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the editor
Risk of intradialytic hypotension in patients on thrice-weekly versus twice-weekly hemodialysis Guangtao Lei a,1, Xia Li b,1, Weiping Tu c, Chengyun Xu c, Zibing Duan c, Xianfeng Wu c,⁎ a b c
Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang, China Department of Nephrology, the First People Hospital of Jining, Jining, China Department of Nephrology, the Second Affiliated Hospital of Nanchang University, Nanchang, China
a r t i c l e
i n f o
Article history: Received 7 April 2014 Accepted 12 April 2014 Available online xxxx Keywords: Intradialytic hypotension Thrice-weekly hemodialysis Risk Twice-weekly hemodialysis
Being afraid of inadequate dialysis, thrice-weekly HD has been regarded as a standard renal replacement therapy (RRT) for ESRD patients [1]. Nevertheless, twice-weekly HD remains prevalent in the developing countries and also could be found in some developed countries [2,3]. Thus far, scarce data are available for the clinical outcomes, especially intradialytic hypotension (IDH), of twice-weekly HD patients. Few studies have used a rigorous definition of IDH according to the European Best Practice Guidelines (EBPG), which defines as both a fall blood pressure and the occurrence of symptoms requiring an intervention [4]. IDH is the most commonly adverse effect of HD [5,6] and is strongly associated with many adverse clinical events [7–9]. A previous study reported that patients on twice-weekly HD suffered from significantly fewer IDH episodes compared with those thrice-weekly HD [10]. Nonetheless, the definition of IDH was markedly different from that of EBPG, which may contribute to bias of their findings. Furthermore, the risk of IDH failed to be evaluated in patients undergoing thrice-weekly HD as compared with those with twice-weekly HD in that study. Therefore, the purpose of this work was to evaluate the risk of IDH in patients on thrice-weekly vs. twice-weekly HD.
⁎ Corresponding author at: Department of Nephrology, the Second Affiliated Hospital of Nanchang University, Minde Road I, Donghu District, Nanchang, Jiangxi Province, China, 330006. Tel.: +86 791 86312551. E-mail address: [email protected] (X. Wu). 1 Contributed equally to this study.
From January 1, 2013, to December 31, 2013, 129 incident and prevalent patients were recruited from a single HD center of the Second Affiliated Hospital of Nanchang University. Enrollment included patients aged ≥18 years who had received HD for N3 months, except those who had undergone peritoneal dialysis (PD) previously, malignant disease or refused to give written consent. This work was a prospective study. Eligible patients were divided into two groups according to nephrologists' recommendation and patients' choice: twice-weekly group and thrice-weekly group. Baseline characteristics, including age, sex, HD vintage, dry weight, urine output, diabetes, pre-existing cardiovascular disease (CVD), hypertension as well as etiology of renal disease were collected at the initiation of entry of this study. Time-dependent parameters included hemoglobin, hematocrit, uric acid, calcium phosphate product, intact parathormone (iPTH), ferritin, albumin, cholesterol and spKt/v (spKt/v). The primary outcome was IDH. Patients were followed up until death, transfer to PD therapy, kidney transplantation, transfer of care from our center or censoring on December 31, 2013. The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University. All patients provided informed consent before study entry. Diagram flow was show in Fig. 1. In our study, 93 (72.1%) were in the twice-weekly group and 36 (27.9%) in the thrice-weekly group. Compared with patients on twice-weekly HD, thrice-weekly HD patients had significantly lower urine output (p b 0.001) but higher calcium phosphate product (p b 0.001, Table 1). During the follow-up, 12 (12.9%) patients developed IDH in the twice-weekly group and 10 (27.8%) in the thrice-weekly group. IDH incidence was significantly higher in the thrice-weekly group as compared to the twice-weekly group [odds ratios 2.60, 95% confidence index (CI) 1.13–3.85, p = 0.044]. Multivariate analysis showed that older age [hazard ratio (HR) 1.03, 95% CI = 1.01–1.07, p = 0.048], higher calcium phosphate product (HR = 1.04, 95% CI = 1.01–1.07, p = 0.042), and thrice-weekly HD (with twice-weekly HD as reference, HR = 2.63, 95% CI = 1.13–3.89, p = 0.047) were independently associated with increased the risk of IDH in this study population (Table 2). On multivariate analysis, older age (HR = 1.02, 95% CI = 1.01–1.07, p = 0.028) and higher calcium phosphate product (HR = 1.10, 95% CI = 1.03–1.18, p = 0.009) were independently risk factors for IDH in thrice-weekly HD patients (Table 3). Table 4 showed that older age (HR = 1.03, 95% CI = 1.01–
http://dx.doi.org/10.1016/j.ijcard.2014.04.140 0167-5273/© 2014 Elsevier Ireland. Ltd. All rights reserved.
Please cite this article as: Lei G, et al, Risk of intradialytic hypotension in patients on thrice-weekly versus twice-weekly hemodialysis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.140
2
G. Lei et al. / International Journal of Cardiology xxx (2014) xxx–xxx
Fig. 1. Flow diagram. PD, peritoneal dialysis; HD,hemodialysis; IDH, intradialytic hypotension.
1.13, p = 0.041), pre-existing CVD (HR = 1.84, 95% CI = 1.06–3.34, p = 0.035) and higher calcium phosphate product (HR = 1.09, 95% CI = 1.03–1.17, p = 0.037) were independently predictors for IDH in those on twice-weekly HD. Fig. 2 showed that a significant difference between IDH and their association with HD frequency was observed, with higher cumulative IDH in patients on thrice-weekly HD (log rank = 13.458, p = 0.005). Patients with thrice-weekly HD had significantly higher IDH incidence than those with twice-weekly HD (HR = 2.47, 95% CI = 1.19–3.69, p = 0.044), when extensive demographics, comorbidities and lab adjustments were made (Table 5). A previous study has reported that patients undergoing twiceweekly HD had fewer IDH episodes compared to those undergoing thrice-weekly HD [10]. However, in that study, the definition of IDH was remarkably different from that defined by the EBPG. Thus, the
Table 2 Hazard ratio of IDH in multivariate Cox regression analysis of all HD patientsa. Total patients (n = 129)
Age (per 1 year increase) Urine output (per 100 mL increase) Diabetes (yes/no) Calcium phosphate productb Albumin (per 1 g/L increase) Thrice-weekly HDc
HR
95% CI
p value
1.03 1.00 1.82 1.04 0.92 2.63
1.01–1.07 0.98–1.01 0.65–5.09 1.01–1.07 0.82–1.02 1.13–3.89
0.048 0.530 0.253 0.042 0.103 0.047
a
Factors, which had a difference in relative risk of events by N 10% (b0.90 or N1.1) in the univariate analysis, were included in the multivariate analysis [13].bPer 10 increase.cReference group was twice-weekly HD. IDH = intradialytic hypotension; HD = hemodialysis; HR = hazard ratio; CI = confidence index.
Table 1 Baseline data of total HD patients.
Age (years) Male (%) HD vintage (months) Dry weight (kg) Urine output (mL/24 h) Diabetes (%) Pre-existing CVD (%) Hypertension (%) Etiology of renal disease (%) Chronic glomerulonephritis (%) Diabetic nephropathy (%) Hypertensive nephrosclerosis (%) Other/unknown (%) Lab measurements Hemoglobin (g/L) Hematocrit (%) Serum uric acid (μmol/L) Calcium phosphate product iPTH (pg/mL) Ferritin (ng/mL) Albumin (g/L) Cholesterol (mmol/L) spKt/v
Total patients (n = 129)
Twice-weekly group (n = 93)
Thrice-weekly group (n = 36)
p value
61.8 ± 14.9 86 (66.7) 12.3(8.4–25.0) 57.8 ± 10.3 400.0(0.0–800.0) 45 (34.9) 29 (22.5) 112(86.8)
61.4 ± 15.9 63 (66.7) 11.4(7.9–22.0) 57.9 ± 9.5 500.0(200.0–1000.0) 29(31.2) 22 (23.7) 78(83.9)
62.9 ± 12.9 23 (63.9) 17.1(10.3–27.3) 57.7 ± 12.4 100.0(0.0–200.0) 16 (44.4) 7 (19.4) 34(94.4)
0.599 0.677 0.072 0.946 b0.001 0.125 0.607 0.111
47 (36.4) 42(32.6) 22(17.1) 18(14.0)
38 (40.9) 25(26.9) 18(19.4) 12(12.9)
11 (25.0) 17(47.2) 4(11.1) 6(16.7)
0.093 0.027 0.264 0.580
90.9 ± 18.3 27.8 ± 11.4 442.7 ± 100.6 47.4 ± 14.3 199.4(124.9–359.4) 247.7(170.6–345.3) 35.8 ± 4.3 3.9 ± 1.0 1.3 ± 0.3
89.4 ± 18.9 27.9 ± 13.1 447.4 ± 112.0 44.1 ± 11.2 175.4(123.4–347.0) 254.4(168.4–344.8) 35.9 ± 4.0 3.9 ± 0.9 1.2 ± 0.3
91.5 ± 11.6 27.4 ± 4.9 430.5 ± 62.0 55.7 ± 15.9 232.5(134.3–407.4) 218.3(174.6–346.5) 35.6 ± 5.0 4.0 ± 1.1 1.3 ± 0.3
0.552 0.870 0.392 b0.001 0.191 0.594 0.793 0.703 0.209
HD, hemodialysis; CVD, cardiovascular disease; iPTH, intact parathormone; spKt/v, single pool Kt/v.
Please cite this article as: Lei G, et al, Risk of intradialytic hypotension in patients on thrice-weekly versus twice-weekly hemodialysis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.140
G. Lei et al. / International Journal of Cardiology xxx (2014) xxx–xxx
3
Table 3 Hazard ratio of IDH in multivariate Cox regression analysis of patients on thrice-weekly HDa. Thrice-weekly group (n = 36)
Age (per 1 year increase) HD vintage (per 1 month increase) Diabetes (yes/no) Pre-existing CVD (yes/no) Calcium phosphate productb
HR
95% CI
p value
1.02 1.01 1.82 1.35 1.10
1.01–1.07 0.99–1.04 0.73–5.31 0.99–3.46 1.03–1.18
0.028 0.235 0.182 0.149 0.009
a Factors, which had a difference in relative risk of events by N 10% (b0.90 or N1.1) in the univariate analysis, were included in the multivariate analysis [13].bPer 10 increase. IDH, intradialytic hypotension; HD, hemodialysis; CVD, cardiovascular disease; HR, hazard ratio; CI, confidence index.
Table 4 Hazard ratio of IDH in multivariate Cox regression analysis of patients on twice-weekly HDa.
Fig. 2. Crude analysis of IDH between twice-weekly HD and thrice-weekly HD (Kaplan– Meier estimates of IDH). IDH, intradialytic hypotension; HD, hemodialysis.
Twice-weekly group (n = 93)
Age (per 1 year increase) Pre-existing CVD (yes/no) Hemoglobin (per 1 g/L increase) Hematocrit (per 1% increase) Calcium phosphate product b Serum ferritin (per 1 ng/mL increase) spKt/v (per 0.1 increase)
HR
95% CI
p value
1.06 1.84 1.02 0.91 1.09 1.00 0.83
1.01–1.13 1.06–3.34 0.90–1.14 0.81–1.03 1.03–1.17 0.99–1.01 0.59–2.13
0.041 0.035 0.771 0.128 0.037 0.218 0.336
a Factors, which had a difference in relative risk of events by N 10% (b0.90 or N1.1) in the univariate analysis, were included in the multivariate analysis [13].bPer 10 increase. IDH, intradialytic hypotension; HD, hemodialysis; CVD, cardiovascular disease; spKt/v, single pool Kt/v; HR, hazard ratio; CI, confidence index.
disparity of IDH definition may contribute to bias of that study findings. In addition, the risk of IDH in that study failed to be investigated in patients with thrice-weekly HD compared with those twice-weekly HD. In our study, patients on thrice-weekly HD had higher IDH hazard (HR = 2.47) than those with twice-weekly HD. One of causes of the results may be: HD per se is not a physiological treatment and is associated with unstable cardiovascular homeostasis [11]. Compared to thrice-weekly HD, a twice-weekly HD has less weekly unstable cardiovascular homeostasis because of the lower frequency of HD, which may potentially benefit the twice-weekly HD. Nonetheless, the underlying mechanisms connecting IDH with HD frequency are still far from being well understood. In our study, pre-existing CVD conveys a higher independent risk of IDH in those undergoing twice-weekly HD (HR = 1.84). Additionally, previous study reported that increasing of calcium concentration in
Table 5 Risk of IDH in thrice-weekly vs. twice-weekly HD. Thrice-weekly group (n = 36)
Unadjusted Model 1 Model 2 Model 3
HR
95% CI
p value
2.61 2.63 2.49 2.47
1.11–3.72 1.14–3.89 1.21–3.91 1.19–3.69
0.049 0.032 0.039 0.044
Note: Reference group is twice-weekly HD (n = 93). Model 1: adjusted for age, sex, dry weight and urine output. Model 2: adjusted for model 1 covariates and diabetes, pre-existing CVD and hypertension. Model 3: adjusted for model 2 covariates and hemoglobin, hematocrit, serum uric acid, calcium phosphate product, iPTH, ferritin, albumin, cholesterol and Kt/v. IDH, intradialytic hypotension; HD, hemodialysis; CVD, cardiovascular disease; iPTH, intact parathormone; spKt/v, single pool Kt/v; HR, hazard ratio; CI, confidence index.
dialysate may protect against IDH in some patients [12]. Results in our study showed that higher calcium phosphate product, as a potentially modifiable treatment-related parameter, was independently associated with increased risk of IDH in HD patients, regardless of HD frequency. Three limitations were noted. First, this was a prospective singlecenter study with a small number of participants and limited followup. Second, we failed to analyze weekly Kt/v in this study. Lastly, patients failed to be randomly assigned into thrice-weekly HD or twice-weekly HD. In conclusion, patients on thrice-weekly HD may be associated with increased risk of IDH as compared to those with twice-weekly HD. Given the global epidemic of ESRD and the escalating financial burden of RRT, our findings have important clinical implications. Acknowledgements We thank all staffs in our HD center to make contribution for data collection, excellent patients care, and so on. References [1] Clinical practice guidelines for hemodialysis adequacy, update 2006. Am J Kidney Dis 2006;48(Suppl. 1):S2–S90. [2] Couchoud C, Kooman J, Finne P, et al. From registry data collection to international comparisons: examples of haemodialysis duration and frequency. Nephrol Dial Transplant 2009;24:217–24. [3] Hanson JA, Hulbert-Shearon TE, Ojo AO, et al. Prescription of twice-weekly hemodialysis in the USA. Am J Nephrol 1999;19:625–33. [4] Kooman J, Basci A, Pizzarelli F, et al. EBPG guideline on haemodynamic instability. Nephrol Dial Transplant 2007;22(Suppl. 2):ii22–44. [5] Davenport A. Intradialytic complications during hemodialysis. Hemodial Int 2006;10:162–7. [6] Davenport A, Cox C, Thuraisingham R. Achieving blood pressure targets during dialysis improves control but increases intradialytic hypotension. Kidney Int 2008;73:759–64. [7] Owen PJ, Priestman WS, Sigrist MK, et al. Myocardial contractile function and intradialytic hypotension. Hemodial Int 2009;13:293–300. [8] Mizumasa T, Hirakata H, Yoshimitsu T, et al. Dialysis-related hypotension as a cause of progressive frontal lobe atrophy in chronic hemodialysis patients: a 3-year prospective study. Nephron Clin Pract 2004;97:c23–30. [9] Shoji T, Tsubakihara Y, Fujii M, Imai E. Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients. Kidney Int 2004;66:1212–20. [10] Lin YF, Huang JW, Wu MS, et al. Comparison of residual renal function in patients undergoing twice-weekly versus three-times-weekly haemodialysis. Nephrology (Carlton) 2009;14:59–64. [11] Lin X, Yan Y, Ni Z, et al. Clinical outcome of twice-weekly hemodialysis patients in shanghai. Blood Purif 2012;33:66–72. [12] Maynard JC, Cruz C, Kleerekoper M, Levin NW. Blood pressure response to changes in serum ionized calcium during hemodialysis. Ann Intern Med 1986;104:358–61. [13] Trivedi H, Xiang Q, Klein JP, et al. Risk factors for non-fatal myocardial infarction and cardiac death in incident dialysis patients. Nephrol Dial Transplant 2009;24:258–66.
Please cite this article as: Lei G, et al, Risk of intradialytic hypotension in patients on thrice-weekly versus twice-weekly hemodialysis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.140
