Associations of hemodialysis dose and session length with mortality risk in Australian and New Zealand patients
2006; Elsevier BV; Volume: 69; Issue: 7 Linguagem: Inglês
10.1038/sj.ki.5000188
ISSN1523-1755
AutoresMark R. Marshall, Berbie Byrne, Peter G. Kerr, Stephen P. McDonald,
Tópico(s)Acute Kidney Injury Research
ResumoThe optimal combination of hemodialysis (HD) dose and session length remains uncertain, and previous studies have not conclusively shown session length to be an important independent determinant of patient mortality. The objective of this study was to examine associations between HD dose and session length with mortality risk using data from the Australian and New Zealand Dialysis and Transplant Registry. Analyses were performed using a prospective inception cohort comprising all incident adult patients treated by thrice-weekly maintenance HD, who commenced renal replacement therapy with HD between 1 April 1997 and 31 March 2004. In all, 6593 patients were identified, of whom 4193 had sufficient data for multivariate analyses. HD dose (single pool fractional clearance of urea, Kt/V) and session length were included in analyses as those recorded 12 months after HD inception to reduce confounding by residual renal function. The outcome examined was patient mortality. Survival analyses included Kaplan–Meier calculations of survival and Cox regression for multivariate analyses. Covariates in Cox models included patient demographics, co-morbid medical conditions at HD inception, and HD operating parameters. After adjustment for covariates and each other, Kt/V of 1.30–1.39 and session length of 4.5–4.9 h were associated with the lowest mortality risk. There was no interaction between HD dose and session length. Thus, the optimal combination for mortality appears to be Kt/V of ≥1.3 and session length of ≥4.5 h. These data suggest a randomized controlled trial to test these hypotheses, and support the inclusion of criteria relating to session length in definitions of adequate HD practice. The optimal combination of hemodialysis (HD) dose and session length remains uncertain, and previous studies have not conclusively shown session length to be an important independent determinant of patient mortality. The objective of this study was to examine associations between HD dose and session length with mortality risk using data from the Australian and New Zealand Dialysis and Transplant Registry. Analyses were performed using a prospective inception cohort comprising all incident adult patients treated by thrice-weekly maintenance HD, who commenced renal replacement therapy with HD between 1 April 1997 and 31 March 2004. In all, 6593 patients were identified, of whom 4193 had sufficient data for multivariate analyses. HD dose (single pool fractional clearance of urea, Kt/V) and session length were included in analyses as those recorded 12 months after HD inception to reduce confounding by residual renal function. The outcome examined was patient mortality. Survival analyses included Kaplan–Meier calculations of survival and Cox regression for multivariate analyses. Covariates in Cox models included patient demographics, co-morbid medical conditions at HD inception, and HD operating parameters. After adjustment for covariates and each other, Kt/V of 1.30–1.39 and session length of 4.5–4.9 h were associated with the lowest mortality risk. There was no interaction between HD dose and session length. Thus, the optimal combination for mortality appears to be Kt/V of ≥1.3 and session length of ≥4.5 h. These data suggest a randomized controlled trial to test these hypotheses, and support the inclusion of criteria relating to session length in definitions of adequate HD practice. The annual mortality rate in hemodialysis (HD) populations is unacceptably high. In the United States (US), it remains consistently higher than that in other developed nations. It has been recently reported that approximately 30% of this increased mortality risk in the US compared to elsewhere is attributable to more severe co-morbid medical burden and older age.1.Goodkin D. Bragg-Gresham J. Koenig K. et al.Association of comorbid conditions and mortality in hemodialysis patients in Europe, Japan, and the United States: The Dialysis Outcomes and Practice Patterns Study (DOPPS).J Am Soc Nephrol. 2003; 14: 3270-3277Crossref PubMed Scopus (594) Google Scholar The majority of this increased risk is therefore likely to result from HD practice patterns. There is in general a lack of critical evidence governing such practice, and adequate HD remains difficult to define and is to a large degree opinion-based. With such accessible and well-defined patients, there is an urgent need for further study to improve outcomes in this population. The interrelated effects of HD dose and session length on patient outcomes have never been satisfactorily resolved. Interest in this area has remained high, especially after the publication of the Hemodialysis (HEMO) Study, which showed that outcomes were not improved with higher doses of dialysis than current consensus standards for patients receiving HD on a conventional short-hour thrice-weekly schedule.2.Eknoyan G. Beck G.J. Cheung A.K. et al.Effect of dialysis dose and membrane flux in maintenance hemodialysis.N Engl J Med. 2002; 347: 2010-2019Crossref PubMed Scopus (1466) Google Scholar One implication of this study is that further improvement in outcomes might necessarily involve more than simply change to dialysis operating parameters within the limitations of this particular schedule.3.Henderson L.W. The inadequacy of Kt/Vurea: a brief history of time.Hemodial Int. 2004; 8: 139-143Crossref PubMed Scopus (2) Google Scholar Increasingly, clinical outcomes research is focusing on unconventional HD regimens characterized by varying combinations of high and low efficiency, longer and shorter session length, and hemeral or nocturnal schedule. Simulations and limited clinical data have determined the impact of these different regimens upon solute control.4.Kooistra M. Vos J. Koomans H. et al.Daily home haemodialysis in The Netherlands: effects on metabolic control, haemodynamics, and quality of life.Nephrol Dial Transplant. 1998; 13: 2853-2860Crossref PubMed Scopus (203) Google Scholar, 5.Woods J. Port F. Orzol S. et al.Clinical and biochemical correlates of starting ‘daily’ hemodialysis.Kidney Int. 1999; 55: 2467-2476Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar, 6.Raj D. Ouwendyk M. Francoeur R. et al.Beta(2)-microglobulin kinetics in nocturnal haemodialysis.Nephrol Dial Transplant. 2000; 15: 58-64Crossref PubMed Scopus (139) Google Scholar, 7.Goldfarb-Rumyantzev A. Cheung A. Leypoldt J.K. Computer simulation of small-solute and middle-molecule removal during short daily and long thrice-weekly hemodialysis.Am J Kidney Dis. 2002; 40: 1211-1218Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar However, there is only limited information regarding clinical outcomes, with most series published out of single centers and none from large multi-center observational datasets.4.Kooistra M. Vos J. Koomans H. et al.Daily home haemodialysis in The Netherlands: effects on metabolic control, haemodynamics, and quality of life.Nephrol Dial Transplant. 1998; 13: 2853-2860Crossref PubMed Scopus (203) Google Scholar, 5.Woods J. Port F. Orzol S. et al.Clinical and biochemical correlates of starting ‘daily’ hemodialysis.Kidney Int. 1999; 55: 2467-2476Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar, 8.Williams A. Chebrolu S. Ing T. et al.Early clinical, quality-of-life, and biochemical changes of ‘daily hemodialysis’ (6 dialyses per week).Am J Kidney Dis. 2004; 43: 90-102Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 9.Pierratos A. Daily nocturnal home hemodialysis.Kidney Int. 2004; 65: 1975-1986Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 10.Andre M. Rembold S. Pereira C. et al.Prospective evaluation of an in-center daily hemodialysis program: results of two years of treatment.Am J Nephrol. 2002; 22: 473-479Crossref PubMed Scopus (32) Google Scholar There is even less known about the optimal HD session length for the thrice-weekly schedule, which is likely to remain the schedule for most HD patients unless studies of unconventional regimens yield conclusive results, and resources are made available to implement them. The most conspicuous features of HD delivery in the US have historically been low HD dose and short session length. Recent data indicate that HD dose is no longer disparate between the US and elsewhere, although HD sessions remain short.11.Port F. Pisoni R. Bragg-Gresham J. et al.DOPPS estimates of patient life years attributable to modifiable hemodialysis treatment practices in the United States.Blood Purif. 2004; 22: 175-180Crossref PubMed Scopus (89) Google Scholar, 12.Goodkin D. Young E. An update on the Dialysis Outcomes and Practice Patterns Study (DOPPS).Contemp Dial Nephrol. 2001; 22: 36-40Google Scholar In Australia and New Zealand, HD practice patterns have evolved independently of the fiscal regulations that have shaped corresponding practice in the US. There is greater variation in HD dose and session length in Australia and New Zealand, and this may allow for the identification of different associations between these parameters and patient outcomes. The objective of this study was to determine the association between both HD dose and session length with mortality risk in a large HD population receiving thrice-weekly treatments, using data from the Australian and New Zealand Dialysis and Transplant (ANZDATA) Registry. In all, 6593 adult patients were identified as being treated with maintenance thrice-weekly HD (on HD both 90 days after commencement and also at 12 months after dialysis inception) in Australia and New Zealand between 1 April 1997 and 31 March 2004. Of these, 4171 patients had sufficient data to be included in modelling. Table 1 summarizes the characteristics of both cohorts. The study cohort was representative of the inception cohort except in two regards. The study cohort had a slightly lower proportion of patients whose primary renal disease was glomerulonephritis, and contained slightly older patients. Among the study cohort, there were 984 deaths recorded over 7228 person-years of follow-up. Of the deaths, 51% were attributed to cardiovascular disease, 12% to infections, and 13% to voluntary dialysis withdrawal.Table 1Clinical characteristics of patientsVariableInception cohort (%)Study cohort (%)Number65934171Country Australia5781 (87.7)3700 (88.7) New Zealand812 (12.3)471 (11.3)Age (years) (median, IQR)58.2 (46.2–68.7)59.9 (48.3–70.7)aP<0.001 and refer to the difference between the inception and study cohorts.Gender Male4093 (62.1)2570 (61.6) Female2500 (37.9)1601 (38.4)Race Caucasian/other5133 (77.8)3215 (77.9) Aboriginal/Torres Islander598 (9.1)419 (10.0) Asian359 (5.5)217 (5.2) Maori/Pacific Islander503 (7.6)320 (7.7)Late referralbReferral for nephrology pre dialysis care <3 months before dialysis inception.1600 (24.3)1046 (25.1)Smoking Current929 (14.1)568 (13.6) Former2712 (41.1)1759 (42.2)Diabetes mellitus Type 1228 (3.5)143 (3.4) Type 22087 (31.7)1442 (34.6)Primary renal disease Glomerulonephritis1967 (29.8)1127 (27.0)cP<0.05. Analgesic nephropathy282 (4.3)169 (4.1) Hypertension/ischemic nephropathy855 (13.0)600 (14.4) Polycystic kidney disease509 (7.7)279 (6.7) Diabetic nephropathy1701 (25.8)1153 (27.6) Other1279 (19.4)843 (20.2)Coronary artery disease2484 (37.7)1646 (39.5)Peripheral vascular disease1659 (25.2)1084 (26.0)Cerebrovascular disease898 (13.6)594 (14.2)Treated hypertension5742 (87.1)3620 (86.8)Lung disease968 (14.7)631 (15.1)BMI (kg/m2) (median, IQR)26.0 (22.8–30.1)25.3 (22.4–29.0)aP<0.001 and refer to the difference between the inception and study cohorts.Hemodialyser flux Low5710 (86.6)3465 (83.1) High883 (13.4)706 (16.9)Dialysis accessdThere were 1645 missing responses. Arteriovenous fistula3786 (77.4)3223 (77.3) Arteriovenous graft706 (10.7)589 (14.1) Central venous catheter456 (6.9)359 (8.6)BMI, body mass index; IQR, interquartile range.a P<0.001 and refer to the difference between the inception and study cohorts.b Referral for nephrology pre dialysis care <3 months before dialysis inception.c P<0.05.d There were 1645 missing responses. Open table in a new tab BMI, body mass index; IQR, interquartile range. The distributions of HD dose and session length within the study cohort are shown in Figure 1. These parameters were not correlated (r=0.027, P=0.08). Figure 2 illustrates HD session length stratified by Kt/V for the study cohort. There was no evidence for an interaction between HD session length and Kt/V in any of the analyses, and each parameter was therefore analyzed separately.Figure 2Distribution of HD session length by categories of Kt/V.View Large Image Figure ViewerDownload (PPT) The most prevalent Kt/V category was ≥1.4. Univariate and multivariate analyses are presented in Table 2. Hazard ratios derived from the final multivariate model are shown in Figure 3. Hemodialyser flux, body mass index, cerebrovascular disease, and chronic lung disease were not found to be significant and independent covariates, and were therefore not included in the multivariate model. After adjustment for patient demographics and co-morbid conditions, Kt/V of 1.30–1.39 was associated with the lowest mortality risk. When further adjusted for HD session length, the relationship between mortality and dose persisted, suggesting that the mechanism for the lower mortality risk with higher Kt/V was not primarily longer session lengths. The fractional polynomial analyses (Figure 4) were similar to the categorical analysis.Table 2Mortality risk according to HD dose categoryModelHD dose Kt/V (n)Hazard ratio (95% confidence intervals)Univariate<1.0 (161)1.59 (0.17–2.17)aP<0.01.1.0–1.19 (705)0.99 (0.81–1.20)1.20–1.29 (857)1.00 (Ref)1.30–1.39 (1072)0.79 (0.65–0.95)bP<0.001.≥1.4 (1376)0.92 (0.77–1.1)Multivariate (excluding adjustment for HD session length)<1.0 (161)1.42 (1.03–1.96)bP<0.001.1.0–1.19 (705)1.03 (0.84–1.25)1.20–1.29 (857)1.00 (Ref)1.30–1.39 (1072)0.79 (0.69–0.99)aP<0.01.≥1.4 (1376)1.42 (1.03–1.96)bP<0.001.Adjusted for HD session length Univariate<1.0 (161)1.54 (1.13–2.11)aP<0.01.1.0–1.19 (705)0.97 (0.79–1.18)1.20–1.29 (857)1.00 (Ref)1.30–1.39 (1072)0.79 (0.66–0.96)cP<0.05.≥1.4 (1376)0.89 (0.75–1.06) Multivariate<1.0 (161)1.42 (1.03–1.97)aP<0.01.1.0–1.19 (705)1.03 (0.84–1.25)1.20–1.29 (857)1.00 (Ref)1.30–1.39 (1072)0.79 (0.65–0.95)cP<0.05.≥1.4 (1376)0.83 (0.69–0.99)cP<0.05.HD, hemodialysis.a P<0.01.b P<0.001.c P<0.05. Open table in a new tab Figure 4Univariate and multivariate fractional polynomial graphs depicting the relationship between both HD session length and dose with mortality risk. The multivariate graphs are fully adjusted for patient demographic and co-morbid medical conditions, and HD session length and dose in the other's respective analyses. Shaded areas indicate 95% confidence intervals.View Large Image Figure ViewerDownload (PPT) HD, hemodialysis. The most prevalent HD session length category was 4.0–4.4 h. Univariate and multivariate analyses are presented in Table 3. After adjustment for patient demographics and co-morbid medical conditions, session length of 4.5–4.9 h was associated with the lowest mortality risk, and <3.5 h the highest. When further adjusted for HD dose, the relationship between session length and mortality persisted, suggesting that the mechanism for the lower mortality risk with session length of 4.5–4.9 h was not primarily larger dose among HD patients receiving longer sessions. The fractional polynomial analyses (Figure 4) were similar to the categorical analysis; whether the mortality risk in the ≥5 h group was further reduced could not be established due to insufficient power.Table 3Mortality risk according to HD session length categoryModelHD session length in hours (n)Hazard ratio (95% confidence intervals)Univariate<3.5 (121)1.75 (1.27–2.40)aP<0.001.3.5–3.9 (187)1.18 (0.88–1.60)4–4.4 (2091)1.00 (Ref)4.5–4.9 (753)0.71 (0.59–0.86)aP<0.001.≥5 (1019)0.72 (0.60–0.86)aP<0.001.Multivariate (excluding adjustment for Kt/V)<3.5 (121)1.69 (1.23–2.32)bP<0.01.3.5–3.9 (187)1.11 (0.83–1.48)4–4.4 (2091)1.00 (Ref)4.5–4.9 (753)0.79 (0.65–0.96)cP<0.05.≥5 (1019)0.99 (0.82–1.18)Adjusted for HD dose Univariate<3.5 (121)1.67 (1.22–2.31)bP<0.01.3.5–3.9 (187)1.19 (0.88–1.60)4–4.4 (2091)1.00 (Ref)4.5–4.9 (753)0.71 (0.59–0.85)aP<0.001.≥5 (1019)0.71 (0.59–0.86)aP<0.001. Multivariate<3.5 (121)1.57 (1.14–2.17)bP<0.01.3.5–3.9 (187)1.09 (0.81–1.46)4–4.4 (2091)1.00 (Ref)4.5–4.9 (753)0.80 (0.66–0.97)cP<0.05.≥5 (1019)1.02 (0.85–1.22)HD, hemodialysis.a P<0.001.b P<0.01.c P<0.05. Open table in a new tab HD, hemodialysis. Characteristics of the study cohort for those treated with long (≥4.5 h) versus short (<4.5 h) sessions are presented in Table 4, and in general those receiving longer HD treatments were more likely to be larger, younger, male, current smokers, of Aboriginal, Maori, and Torres Strait and Pacific Island descent, and have diabetes mellitus. We specifically sought, but could not formally demonstrate, a statistical interaction between session length and body mass index (BMI) in the final regression model (interaction HD session length × BMI P=0.22). The issue was further explored by creating categories allowing comparisons of all combinations of BMI categories and session length in the multivariate model (Figure 5). Examined in this manner, the association of longer HD sessions with reduced mortality was seen among those in middle and higher BMI groups, but not in the lowest BMI group.Table 4Clinical characteristics of the study cohort compared by HD session length categoryVariable<4.5 h (%)≥4.5 h (%)Number23991722Country Australia2191 (91.3)1509 (85.2)aP<0.001 and refer to the difference between the subgroups receiving longer and shorter HD treatments. New Zealand208 (8.7)263 (14.8)Age (years) (median, IQR)65.4 (53.2–73.6)58.1 (47.1–68.2)aP<0.001 and refer to the difference between the subgroups receiving longer and shorter HD treatments.Gender Male1299 (54.1)1271 (71.7)aP<0.001 and refer to the difference between the subgroups receiving longer and shorter HD treatments. Female1100 (45.9)501 (28.3)Race Caucasian/other1999 (83.3)1216 (68.6)aP<0.001 and refer to the difference between the subgroups receiving longer and shorter HD treatments. Aboriginal/Torres Islander152 (6.3)267 (15.1) Asian137 (5.7)80 (4.5) Maori/Pacific Islander111 (4.6)209 (11.8)Late referralbReferral for nephrology pre dialysis care <3 months before dialysis inception.566 (23.6)480 (27.1)cP<0.05.Smoking Current301 (12.6)267 (15.1)aP<0.001 and refer to the difference between the subgroups receiving longer and shorter HD treatments. Former976 (40.7)783 (44.2)Diabetes mellitus Type 187 (3.6)56 (3.2)aP<0.001 and refer to the difference between the subgroups receiving longer and shorter HD treatments. Type 2699 (29.1)742 (41.9)Primary renal disease Glomerulonephritis623 (26.0)504 (28.4)aP<0.001 and refer to the difference between the subgroups receiving longer and shorter HD treatments. Analgesic nephropathy119 (5.0)50 (2.8) Hypertension/ischemic nephropathy412 (17.2)188 (10.6) Polycystic kidney disease155 (6.5)124 (7.0) Diabetic nephropathy562 (23.4)591 (33.4) Other528 (22.0)315 (17.8)Coronary artery disease979 (40.8)667 (37.6)cP<0.05.Peripheral vascular disease617 (25.7)467 (26.4)Cerebrovascular disease343 (14.3)251 (14.2)Treated hypertension2399 (85.9)1559 (87.9)Lung disease363 (15.1)268 (15.1)BMI (kg/m2) (median, IQR)24.9 (22.0–28.6)27.8 (24.2–32.4)aP<0.001 and refer to the difference between the subgroups receiving longer and shorter HD treatments.Hemodialyser flux Low2030 (84.6)1435 (81.0)dP<0.01. High369 (15.4)337 (19.0)Dialysis accesseThere were 1645 missing responses. Arteriovenous fistula1832 (76.4)1391 (78.5)dP<0.01. Arteriovenous graft332 (13.8)257 (14.5) Central venous catheter235 (9.8)124 (7.0)BMI, body mass index; IQR, interquartile range.a P<0.001 and refer to the difference between the subgroups receiving longer and shorter HD treatments.b Referral for nephrology pre dialysis care <3 months before dialysis inception.c P<0.05.d P<0.01.e There were 1645 missing responses. Open table in a new tab BMI, body mass index; IQR, interquartile range. It seems axiomatic that more dialysis should provide better outcomes, and there are few who would consider uremic toxicity to be abrogated by the current standard of short-hour thrice-weekly HD. However, optimal HD practice does remain uncertain. There is expert consensus about HD dose in the Kidney Disease Outcomes Quality Initiative and European Best Practice Guidelines,13.National Kidney Foundation K/DOQI Clincal Practice Guidelines for Hemodialysis Adequacy, 2000.Am J Kidney Dis. 2001; 37: S7-S64Google Scholar, 14.European Dialysis and Transplant Association – European Renal Association European best practice guidelines for haemodialysis.Nephrol Dial Transplant. 2002; 17: 17-31Google Scholar and also in the Caring for Australians with Renal Impairment guidelines under development for Australian and New Zealand chronic kidney disease patients (www.kidney.org.au/cari). In contrast, there is no such consensus about HD session length. The recommendations of the Caring for Australians with Renal Impairment guidelines for well-powered, statistically robust observational analyses have led to these analyses of the ANZDATA Registry. The findings of this study support the minimum standards for HD dose advocated by the aforementioned consensus guidelines. However, the crucial finding in this study was that shorter HD session length was associated with higher mortality risk, independently of HD dose. This implies that the evaluation of dialysis adequacy by HD dose alone may be insufficient to optimize outcomes, and that adequate dialysis may be characterized by HD session length of 4.5 h or longer, irrespective of dose. This paradigm has enormous implications for both HD providers and patients. The relative effects of HD dose and session length on patient outcomes were originally explored in the National Cooperative Dialysis Study.15.Lowrie E. Laird N. Parker T. et al.Effect of dialysis prescription on patient morbidity.N Engl J Med. 1981; 305: 1176-1180Crossref PubMed Scopus (565) Google Scholar This study showed that small solute control was a more important determinant of patient morbidity than HD session length. The study did in fact suggest a causal relationship between shorter dialysis and excess patient morbidity, although it was not sufficiently different from chance (P=0.056) to be regarded as significant. As a result, HD session length has often not been considered by both researchers and clinicians in the endeavor to define and deliver adequate dialysis. To our knowledge, there have been no studies other than the National Cooperative Dialysis Study that have addressed the issue of HD dose and session length in a definitive manner. However, a number of observational studies have provided support for both dose and length as determinants of patient mortality. Single-center experience from Tassin, France has shown superior surrogate and actual patient outcomes with longer HD session lengths.16.Innes A. Charra B. Burden R. et al.The effect of long, slow haemodialysis on patient survival.Nephrol Dial Transplant. 1999; 14: 919-922Crossref PubMed Scopus (80) Google Scholar, 17.Charra B. Hurot J.-M. Chazot C. et al.Comparison of survival data.Kidney Int. 2000; 58: 901-902Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar The most compelling multi-center observations have been made using registry-sourced data from a 1993 Japanese cohort, in which HD session length of 5.0–5.5 h was shown to be independently associated with the lowest mortality risk (P<0.01), even when analyses were adjusted for Kt/V.18.Shinzato T. Nakai S. Akiba T. et al.Survival in long-term haemodialysis patients: results from the annual survey of the Japanese Society for Dialysis Therapy.Nephrol Dial Transplant. 1997; 12: 884-888Crossref PubMed Scopus (93) Google Scholar Observations more applicable to US and European populations have been made using US patient cohorts from the 1980s, including two studies in which HD session length shorter than 3.5 h was independently associated with up to approximately doubled mortality risk compared to longer sessions, although neither analysis was adjusted for HD dose.19.Held P. Levin N. Bovbjerg R. et al.Mortality and duration of hemodialysis treatment.JAMA. 1991; 265: 871-875Crossref PubMed Scopus (212) Google Scholar, 20.Lowrie E.G. Lew N.L. Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities.Am J Kidney Dis. 1990; 15: 458-482Abstract Full Text PDF PubMed Scopus (1652) Google Scholar Most recently, the Dialysis Outcome and Practice Patterns Study has presented various analyses using a large cohort of Japanese, US and European patients, in which HD session length shorter than 3.5 h was shown to be independently associated with a 33% higher mortality risk (P=0.004), even when analyses were adjusted for Kt/V.21.Saran R. Bragg-Gresham C. Coombe V. et al.High ultrafiltration rates are associated with poor outcomes in hemodialysis patients: The Dialysis Outcomes and Practice Patterns Study (DOPPS).J Am Soc Nephrol. 2003; 14: 234ACrossref PubMed Scopus (53) Google Scholar The data from this study confirm that HD delivery in Australia and New Zealand is characterized by relatively high delivered HD dose, achieved by longer HD treatments rather than higher blood flow rates. HD session length averaged 263 min and blood flow rate 294 ml/min, as compared with 213 min and 401 ml/min in the US and 234 min and 296 ml/min in Europe.12.Goodkin D. Young E. An update on the Dialysis Outcomes and Practice Patterns Study (DOPPS).Contemp Dial Nephrol. 2001; 22: 36-40Google Scholar, 22.Hecking E. Bragg-Gresham J. Rayner H. et al.Haemodialysis prescription, adherence and nutritional indicators in five European countries: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).Nephrol Dial Transplant. 2003; 19: 100-107Crossref Scopus (118) Google Scholar This HD practice pattern can be attributed to two factors particular to Australia and New Zealand. Firstly, the higher prevalence of home hemodialysis in Australia and New Zealand (stable at approximately 14 and 25% of HD patients, respectively23.Russ G. ANZDATA Registry Report 2003. Australia and New Zealand Dialysis and Transplant Registry, Adelaide, Australia2003Google Scholar) may potentially dilute the effect of scheduling restraints within facilities that so often lead to shortening of hours. Secondly, the prevailing opinion among nephrologists in Australia and New Zealand is that HD session length is at least as, if not more, important than dose: many centers do not prescribe HD treatments of less than 5 h, and those dialyzing their patients for longer hours often do not measure HD dose. There are several possible mechanisms for improved outcomes with longer sessions. Importantly, our analyses have confirmed that the effect of longer HD session length on mortality in this study was not as a result of statistical confounding by BMI. If anything, the effect of session length is more marked among those with higher BMI. Other studies have shown that longer HD sessions result in greater removal of larger molecules,7.Goldfarb-Rumyantzev A. Cheung A. Leypoldt J.K. Computer simulation of small-solute and middle-molecule removal during short daily and long thrice-weekly hemodialysis.Am J Kidney Dis. 2002; 40: 1211-1218Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar and improved phosphate and bicarbonate control,24.Charra B. Chazot C. Jean G. et al.Long, slow dialysis.Miner Eletcrolyte Metb. 1999; 25: 391-396Crossref PubMed Scopus (33) Google Scholar even for a given amount of small solute removal.25.Mactier R. Madi A. Allam B. Comparison of high-efficiency and standard haemodialysis providing equal urea clearances by partial and total dialysate quantification.Nephrol Dial Transplant. 1997; 12: 1182-1186Crossref PubMed Scopus (11) Google Scholar, 26.Johnsson E. Attman P. Samuelsson O. et al.Improved clearance of iohexol with longer haemodialysis despite similar Kt/V for urea.Nephrol Dial Transplant. 1999; 14: 2407-2412Crossref PubMed Scopus (11) Google Scholar, 27.Vaithilingam I. Polkinghorne K. Atkins R. et al.Time and exercise improve phosphate removal in hemodialysis patients.Am J Kidney Dis. 2004; 43: 85-89Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar In addition, less intradialytic hemodynamic instability allows more consistent achievement of dry weight, better blood pressure control, and probably less sympathetic hyperactivity.28.Charra B. Calemard M. Laurent G. Importance of treatment time and blood pressure control in achieving long-term survival on dialysis.Am J Nephrol. 1996; 16: 35-44Crossref PubMed Scopus (187) Google Scholar, 29.McGregor D. Buttimore A. Lynn K. et al.A comparative study of blood pressure control with short in-center versus long home hemodialysis.Blood Purif. 2001; 19: 293-300Crossref PubMed Scopus (60) Google Scholar Despite these findings, it is important to note that both left ventricular hypertrophy and dialysis-related amyloidosis still affect patients receiving longer thrice-weekly HD treatments,30.McGregor D. 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