Treatment frequency and mortality among incident hemodialysis patients in the United States comparing incremental with standard and more frequent dialysis
2016; Elsevier BV; Volume: 90; Issue: 5 Linguagem: Inglês
10.1016/j.kint.2016.05.028
ISSN1523-1755
AutoresAnna Mathew, Yoshitsugu Obi, Connie M. Rhee, Joline L.T. Chen, Gaurang Shah, Wei Ling Lau, Csaba P. Kövesdy, Rajnish Mehrotra, Kamyar Kalantar‐Zadeh,
Tópico(s)Central Venous Catheters and Hemodialysis
ResumoMost patients with end-stage renal disease in the United States are initiated on thrice-weekly hemodialysis (HD) regimens. However, an incremental approach to HD may provide several patient benefits. We tested whether initiation of incremental HD does or does not compromise survival compared with a conventional HD regimen. The survival of 434 incremental, 50,162 conventional, and 160 frequent HD patients were compared using Cox regression analysis after matching for demographic and comorbid factors in a longitudinal national cohort of adult incident HD patients enrolled between January 2007 and December 2011. Sensitivity analysis included adjustment for residual kidney function. After adjustment for residual kidney function, all-cause mortality was not significantly different in the incremental compared with conventional HD group (hazard ratio 0.88, 95% confidence interval 0.72–1.08), but was higher in the frequent compared with the conventional HD group (hazard ratio, 1.56, 95% confidence interval 1.21–2.03). The comorbidity burden modified the association of treatment frequency and mortality, with higher comorbidity associated with higher mortality in the incremental HD group (hazard ratio, 1.77, 95% confidence interval 1.20–2.62) for a Charlson Comorbidity Index of ≥5. Thus, among incident HD patients with low or moderate comorbid disease, survival was similar for patients initiated on an incremental or conventional HD regimen. Clinical trials are needed to examine the safety and effectiveness of incremental HD and the selected patient populations who may benefit from an incremental approach to HDs initiation. Most patients with end-stage renal disease in the United States are initiated on thrice-weekly hemodialysis (HD) regimens. However, an incremental approach to HD may provide several patient benefits. We tested whether initiation of incremental HD does or does not compromise survival compared with a conventional HD regimen. The survival of 434 incremental, 50,162 conventional, and 160 frequent HD patients were compared using Cox regression analysis after matching for demographic and comorbid factors in a longitudinal national cohort of adult incident HD patients enrolled between January 2007 and December 2011. Sensitivity analysis included adjustment for residual kidney function. After adjustment for residual kidney function, all-cause mortality was not significantly different in the incremental compared with conventional HD group (hazard ratio 0.88, 95% confidence interval 0.72–1.08), but was higher in the frequent compared with the conventional HD group (hazard ratio, 1.56, 95% confidence interval 1.21–2.03). The comorbidity burden modified the association of treatment frequency and mortality, with higher comorbidity associated with higher mortality in the incremental HD group (hazard ratio, 1.77, 95% confidence interval 1.20–2.62) for a Charlson Comorbidity Index of ≥5. Thus, among incident HD patients with low or moderate comorbid disease, survival was similar for patients initiated on an incremental or conventional HD regimen. Clinical trials are needed to examine the safety and effectiveness of incremental HD and the selected patient populations who may benefit from an incremental approach to HDs initiation. In the United States, there are >450,000 prevalent patients with end-stage renal disease treated with maintenance dialysis, with ∼114,800 patients who newly initiated hemodialysis (HD) as of 2012.1Saran R. Li Y. Robinson B. US Renal Data System 2014 annual data report: epidemiology of kidney disease in the United States.Am J Kidney Dis. 2015; 66: S1-S306PubMed Google Scholar Most HD patients are conventionally prescribed a standard thrice-weekly schedule with little individualization of the initial HD regimen.2Rhee C.M. Unruh M. Chen J. et al.Infrequent dialysis: a new paradigm for hemodialysis initiation.Semin Dial. 2013; 26: 720727Google Scholar, 3Blagg C.R. Hemodialysis 1991.Blood Purif. 1992; 10: 22-29Crossref PubMed Scopus (5) Google Scholar, 4Kalantar-Zadeh K. Casino F.G. Let us give twice-weekly hemodialysis a chance: revisiting the taboo.Nephrol Dial Transplant. 2014; 29: 1618-1620Crossref PubMed Scopus (41) Google Scholar Dialysis patients have a 6 to 8 times higher mortality risk than age-matched Medicare patients in the general population,1Saran R. Li Y. Robinson B. US Renal Data System 2014 annual data report: epidemiology of kidney disease in the United States.Am J Kidney Dis. 2015; 66: S1-S306PubMed Google Scholar with the highest risk observed during the first 6 months after HD initiation.5Lukowsky L.R. Kheifets L. Arah O.A. et al.Patterns and predictors of early mortality in incident hemodialysis patients: new insights.Am J Nephrol. 2012; 35: 548-558Crossref PubMed Scopus (90) Google Scholar Many potential risk factors may explain this early high mortality, such as a lack of predialysis nephrology care, a lack of permanent vascular accesses, and preexisting cardiovascular disease or other coexisting medical illnesses.6Bradbury B.D. Fissell R.B. Albert J.M. et al.Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).Clin J Am Soc Nephrol. 2007; 2: 89-99Crossref PubMed Scopus (376) Google Scholar However, the impact of an abrupt transition to a "full-dose" thrice-weekly HD regimen versus a gradual transition by incrementally increasing the HD prescription over several months on mortality risk has not been examined in controlled trials. Randomized, controlled trials of a higher dialysis dose or frequency have shown inconsistent results7Eknoyan 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 (1576) Google Scholar, 8Lowrie E.G. Laird N.M. Parker T.F. Sargent J.A. Effect of the hemodialysis prescription of patient morbidity: report from the National Cooperative Dialysis Study.N Engl J Med. 1981; 305: 1176-1181Crossref PubMed Scopus (605) Google Scholar, 9Chertow G.M. Levin N.W. Beck G.J. et al.In-center hemodialysis six times per week versus three times per week.N Engl J Med. 2010; 363: 2287-2300Crossref PubMed Scopus (823) Google Scholar, 10Chertow G.M. Levin N.W. Beck G.J. et al.Long-term effects of frequent in-center hemodialysis.J Am Soc Nephrol. 2016; 27: 1830-1836Crossref Scopus (80) Google Scholar, 11Rocco M.V. Lockridge Jr., R.S. Beck G.J. et al.The effects of frequent nocturnal home hemodialysis: The Frequent Hemodialysis Network Nocturnal Trial.Kidney Int. 2011; 80: 1080-1091Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar, 12Rocco M.V. Daugirdas J.T. Greene T. et al.Long-term effects of frequent nocturnal hemodialysis on mortality: the Frequent Hemodialysis Network (FHN) Nocturnal Trial.Am J Kidney Dis. 2015; 66: 459-468Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar and may accelerate residual kidney function (RKF) decline.13Daugirdas J.T. Greene T. Rocco M.V. et al.Effect of frequent hemodialysis on residual kidney function.Kidney Int. 2013; 83: 949-958Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar An incremental approach to HD initiation may offer many potential benefits to patients, including better preservation of an arteriovenous fistula, reduced cost, and preservation of RKF. Less frequent (i.e., twice weekly) HD has been associated with greater preservation of RKF after initiation of HD,14Lin Y.F. Huang J.W. Wu M.S. et al.Comparison of residual renal function in patients undergoing twice-weekly versus three-times-weekly haemodialysis.Nephrology (Carlton). 2009; 14: 59-64Crossref PubMed Scopus (85) Google Scholar, 15Zhang M. Wang M. Li H. et al.Association of Initial Twice-Weekly Hemodialysis Treatment with Preservation of Residual Kidney Function in ESRD Patients.Am J Nephrol. 2014; 40: 140-150Crossref PubMed Scopus (91) Google Scholar, 16Obi Y. Streja E. Rhee C.M. et al.Incremental hemodialysis, residual kidney function, and mortality risk in incident dialysis patients: a cohort study.Am J Kidney Dis. 2016 Feb 9; ([e-pub ahead of print] http://dx.doi.org/10.1053/j.ajkd.2016.01.008, accessed May 10, 2016)Google Scholar and higher RKF is associated with better patient survival in both PD and HD patients.17Bargman J.M. Thorpe K.E. Churchill D.N. Group C.P.D.S. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study.J Am Soc Nephrol. 2001; 12: 2158-2162PubMed Google Scholar, 18Shemin D. Bostom A.G. Laliberty P. Dworkin L.D. Residual renal function and mortality risk in hemodialysis patients.Am J Kidney Dis. 2001; 38: 85-90Abstract Full Text Full Text PDF PubMed Scopus (248) Google Scholar Preservation of RKF may play a key role in the potential association of less frequent HD and survival. This may be of particular importance among incident HD patients because many patients have substantial RKF when transitioning to end-stage renal disease.16Obi Y. Streja E. Rhee C.M. et al.Incremental hemodialysis, residual kidney function, and mortality risk in incident dialysis patients: a cohort study.Am J Kidney Dis. 2016 Feb 9; ([e-pub ahead of print] http://dx.doi.org/10.1053/j.ajkd.2016.01.008, accessed May 10, 2016)Google Scholar We examined a 5-year nationally representative cohort of incident HD patients to determine the outcome of mortality with a conventional HD treatment regimen compared with incremental or frequent HD regimen. We hypothesized that initiation of HD with an incremental approach does not compromise survival compared with a conventional HD regimen. The final entire study cohort comprised of 87,718 patients from 1737 facilities including 682 incremental (twice weekly or less) HD patients from 444 facilities and 201 frequent (≥4 times weekly) HD patients from 158 facilities (Supplementary Table S1). Compared with the conventional HD patients, the incremental HD patients tended to be older and non-Hispanic white and to have less comorbid burden, whereas the frequent HD patients tended to be younger, male, and non-Hispanic white and to have higher likelihood of having a central venous catheter and a higher comorbid burden (standardized difference >0.1). The final matched cohort included 434 incremental HD patients, 50,162 conventional HD patients, and 160 frequent HD patients (Table 1). Even after matching based on age, sex, race, ethnicity, Charlson Comorbidity Index (CCI) category and the use of central venous catheter access, the frequent HD group compared with the conventional HD group had a higher prevalence of fluid overload (64% vs. 6%), greater weekly percentage of interdialytic weight gain (%IDWG) (9.5% vs. 7.7%), and larger body mass index (30.6 kg/m2 vs. 26.8 kg/m2). Although the prevalence of missing data on renal urea clearance (CLurea) was high (65%), available data showed that the frequent HD group had less renal CLurea (1.9 ml/min per 1.73 m2 vs. 3.1 ml/min per 1.73 m2). Conversely, the conventional HD group compared with the incremental HD group had less %IDWG (5.8% vs. 7.7%) and greater renal CLurea (5.4 ml/min per 1.73 m2 vs. 3.1 ml/min per 1.73 m2). In support of greater renal CLurea in the incremental HD group, creatinine (4.4 mg/dl vs. 5.9 mg/dl) and serum phosphorus (4.3 mg/dl vs. 5.0 mg/dl) were both lower in the incremental HD group compared with the conventional HD group. Figure 1 displays the quarterly-averaged treatment frequency per week and treatment time per session in the incremental HD, conventional HD, and frequent HD groups, with separation between groups maintained throughout the follow-up period.Table 1Baseline characteristics by treatment regimen in the matched cohort of 50,756 incident HD patientsVariableConventionalHD, %n = 50,162FrequentHD, %n = 160Std.Diff.IncrementalHD, %n = 434Std.Diff.Charlson Comorbidity Index3 (IQR, 2–4)3 (IQR, 3–4)0.033 (IQR, 3–4)0.01 2 (renal disease only)24240240 3–462620620 577070 666060 ≥711010Age (yr)63 ± 1362 ± 140.0664 ± 130.04Male (%)65650650Race (%) Non-Hispanic white58580580 Non-Hispanic black29290290 Others12120110.02Medicare as primary insurance (%)54530.03490.10Central venous catheter use (%)84840840Primary disease (%) Diabetic nephropathy49460.06430.11 Hypertensive nephrosclerosis28210.17290.01 Glomerulonephritis8140.17110.09 Polycystic kidney disease110.0530.11 Others13190.15140.03Comorbidities (%) Cardiovascular disease28360.18310.06 Fluid overload664>0.970.03Body mass index (kg/m2)26.8 (IQR, 23.1–31.9)30.6 (IQR, 24.6–37.6)0.3826.3 (IQR, 22.8– 30.5)0.17Postdialysis body weight (kg)77 (IQR, 65–92)91 (IQR, 70–116)0.3677 (IQR, 64–91)0.15Weekly %IDWG7.7 ± 3.59.5 ± 3.80.505.8 ± 3.20.54Single-pool Kt/V1.38 ± 0.301.27 ± 0.340.371.36 ± 0.330.09Renal CLurea (ml/min per 1.73 m2)3.1 (IQR, 1.8–4.8)1.9 (IQR, 1.3–3.2)0.485.4 (IQR, 3.1–.3)0.88Laboratory variables Hemoglobin (g/dl)11.3 ± 1.210.6 ± 1.10.5811.0 ± 1.20.24 Albumin (mg/dl)3.54 ± 0.453.47 ± 0.440.183.56 ± 0.520.04 Creatinine (mg/dl)5.9 ± 2.35.7 ± 2.60.074.4 ± 2.00.68 Calcium (mg/dl)9.1 ± 0.69.0 ± 0.40.149.1 ± 0.50.01 Phosphorus (mg/dl)5.0 ± 1.24.8 ± 1.30.124.3 ± 1.00.62 Intact PTH (pg/ml)321 (IQR, 205–492)275 (IQR, 187–443)0.20253 (IQR, 321–427)0.24 Iron saturation (%)23 ± 919 ± 70.4923 ± 100.05 Ferritin (pg/nl)270 (IQR, 158– 460)256 (IQR, 138–418)0.10287 (IQR, 270– 511)0.11 Bicarbonate (mmol/l)23.7 ± 2.824.1 ± 2.70.1324.3 ± 3.20.19CLurea, urea clearance; HD, hemodialysis; %IDWG, percentage of interdialytic weight gain; IQR, interquartile range; PTH, parathyroid hormone; Std. Diff., standardized difference.Values are expressed as mean ± SD, median (IQR), or percentage, as appropriate. Data are based on weighted match according to age, sex, race, central venous catheter as vascular access, and the Charlson Comorbidity Index.Data on laboratory tests were extracted during the first 91 days of dialysis, and those except for ferritin and iPTH were further restricted to the initial thrice-weekly HD period before starting infrequent or frequent HD.Standardized differences were calculated against the conventional HD group; 0.8, 0.5, and 0.2 were considered large, medium, and small differences, and ≥0.1 was defined as meaningful imbalance.The frequency of missing data was <2% for most laboratory tests, except for iron saturation (3%), creatinine (6%), and renal CLurea (62%).Conversion factors for units: albumin and hemoglobin in g/dl to g/l, 10; creatinine in mg/dl to mmol/l, 88.4; calcium in mg/dl to mmol/l, 0.2495; phosphorus in mg/dl to mmol/l, 0.3229. No conversion was necessary for ferritin in ng/ml and mg/l. Open table in a new tab CLurea, urea clearance; HD, hemodialysis; %IDWG, percentage of interdialytic weight gain; IQR, interquartile range; PTH, parathyroid hormone; Std. Diff., standardized difference. Values are expressed as mean ± SD, median (IQR), or percentage, as appropriate. Data are based on weighted match according to age, sex, race, central venous catheter as vascular access, and the Charlson Comorbidity Index. Data on laboratory tests were extracted during the first 91 days of dialysis, and those except for ferritin and iPTH were further restricted to the initial thrice-weekly HD period before starting infrequent or frequent HD. Standardized differences were calculated against the conventional HD group; 0.8, 0.5, and 0.2 were considered large, medium, and small differences, and ≥0.1 was defined as meaningful imbalance. The frequency of missing data was <2% for most laboratory tests, except for iron saturation (3%), creatinine (6%), and renal CLurea (62%). Conversion factors for units: albumin and hemoglobin in g/dl to g/l, 10; creatinine in mg/dl to mmol/l, 88.4; calcium in mg/dl to mmol/l, 0.2495; phosphorus in mg/dl to mmol/l, 0.3229. No conversion was necessary for ferritin in ng/ml and mg/l. Among 434 patients in the incremental HD group, 155 patients (36%) transitioned to conventional treatment frequency (i.e., 2.5–3.5 per week) after a median of 3 quarters (interquartile range [IQR], 1–5) on less treatment schedule (i.e., 3.5 per week). During the 91 days before transition to thrice-weekly HD, mean weekly interdialytic weight gain was 12.2 ± 4.4% and mean serum concentrations of creatinine and phosphorus were 6.7 ± 2.5 mg/dl and 5.1 ± 1.4 mg/dl, respectively.Table 2Characteristics during the 91 days before transition to thrice-weekly HD schedule among patients in the incremental HD groupCharacteristicsIncremental HD155 (36%)Frequent HD81 (49%)Time to transition to thrice-weekly HD (quarter)3 (1–5)1 (1–3)Weekly IDWG (%body weight)6.6 ± 3.212.2 ± 4.4Hemoglobin (g/dl)10.9 ± 1.211.3 ± 0.9Albumin (g/dl)3.7 ± 0.43.6 ± 0.5Creatinine (mg/dl)6.4 ± 3.26.7 ± 2.5Corrected calcium (mg/dl)8.9 ± 0.79.1 ± 0.4Phosphorus (mg/dl)5.2 ± 1.15.1 ± 1.4Intact PTH (pg/ml)299 (182–375)261 (155–363)Iron saturation (%)26 ± 926 ± 10Ferritin (ng/ml)500 (326–792)417 (248–708)Bicarbonate (mmol/l)22.4 ± 2.923.2 ± 2.9HD, hemodialysis; IDWG, interdialytic weight gain; PTH, parathyroid hormone.Values are expressed as mean ± SD, median (IQR), or percentage, as appropriate.Data are based on weighted match according to age, sex, race, central venous catheter as vascular access, and the Charlson Comorbidity Index.The frequency of missing data was <2% for most laboratory tests, except for ferritin (3%).Conversion factors for units: albumin and hemoglobin in g/dl to g/l, 10; creatinine in mg/dl to mmol/l, 88.4; calcium in mg/dl to mmol/l, 0.2495; phosphorus in mg/dl to mmol/l, 0.3229. No conversion was necessary for ferritin in ng/ml and mg/l. Open table in a new tab HD, hemodialysis; IDWG, interdialytic weight gain; PTH, parathyroid hormone. Values are expressed as mean ± SD, median (IQR), or percentage, as appropriate. Data are based on weighted match according to age, sex, race, central venous catheter as vascular access, and the Charlson Comorbidity Index. The frequency of missing data was 0% to 3%, and >3% at 1293 (74%), 288 (17%), and 156 (9%) facilities, respectively (Table 3). The median prevalence of urine collection during the first 91 days of dialysis was 33% (IQR, 11%–57%), 42% (IQR, 20%–63%), and 56% (IQR, 37%–64%) among those facilities with the prevalence of the incremental HD regimen 0%, >0% to 3%, and >3%, respectively. There was a significant trend toward a higher prevalence of urine collection as facility prevalence of patients with the incremental HD regimen increased (Ptrend < 0.001). Compared with facilities that never prescribed incremental HD, those facilities with >0% to 3% and >3% prevalence of the incremental HD had 1.5% (95% CI 0.1%–2.9%) and 7.3% (95% CI 5.3%–9.5%) higher median renal CLurea levels during the first 91 days of dialysis (Ptrend < 0.001) and also had higher a likelihood of prescribing frequent HD (odds ratio 1.75 [95% CI 1.30–2.37] and odds ratio 1.96 [95% CI 1.25–3.07]), respectively. Conversely, the prevalence of a frequent HD regimen among incident dialysis patients was not associated with the prevalence of urine collection or median renal CLurea levels during the first 91 days of dialysis (Ptrend = 0.12 and 0.30, respectively) (Supplementary Table S2). Compared with facilities that never prescribed frequent HD, the likelihood of prescribing incremental HD was higher in those facilities with >0% to 2% (odds ratio 1.65 [95% CI 1.36–2.01]) but not in those with >2% patients with frequent HD (odds ratio 1.31 [95% CI 0.88–1.94]).Table 3Facility-level baseline characteristics according to the prevalence of the incremental regimen among 87,718 patients with end-stage renal disease who started hemodialysis from January 1, 2007 to December 31, 2011 at 1737 facilitiesPrevalence of incident HD patients with the incremental regimen0%(n = 1293; 74%)>0% to 3%(n = 288; 17%)>3%(n = 156; 9%)Total no. of incident HD patients40 (IQR, 19–64)72 (IQR, 52–93)aP < 0.05 compared with the 0% group.32 (IQR, 20–58)Patients with baseline RKF data33% (IQR, 11%–57%)42% (IQR, 20%–63%)aP < 0.05 compared with the 0% group.56% (IQR, 37%–74%)aP < 0.05 compared with the 0% group.Median renal CLurea (ml/min per 1.73 m2)3.5 (IQR, 2.9–4.3)3.6 (IQR, 3.2–4.1)3.9 (IQR, 3.4–4.4)aP < 0.05 compared with the 0% group.Ever prescribed frequent HD (%)6%20%aP < 0.05 compared with the 0% group.16%aP < 0.05 compared with the 0% group.HD, hemodialysis; CLurea, renal urea clearance; IQR, interquartile range; RKF, residual kidney function.a P < 0.05 compared with the 0% group. Open table in a new tab HD, hemodialysis; CLurea, renal urea clearance; IQR, interquartile range; RKF, residual kidney function. In the matched cohort, 13,175 conventional HD patients, 91 incremental HD patients, and 62 frequent HD patients died during follow-up. For conventional HD, incremental HD, and frequent HD groups, the mortality rates were 17.8 per 100 patient-years, 17.6 per 100 patient-years and 35.2 per 100 patient-years, respectively. Kaplan-Meier survival estimates were lower in the frequent HD group compared with the incremental HD and conventional HD groups in both the entire (Supplementary Figure S1) and matched (Figure 2) cohorts. In the matched cohort, all-cause mortality was not significantly different in the incremental HD group compared with the conventional HD group. However, all-cause mortality was significantly higher in the frequent HD group compared with the conventional HD group. These findings remained robust across all adjustment models (Figure 3). Even with additional adjustment for RKF, the incremental HD group had no difference in survival compared with conventional HD group (HR 0.88, 95% CI 0.72–1.08) and the frequent HD group had significantly higher mortality compared with conventional HD (HR 1.56, 95% CI 1.21–2.03).Figure 3Adjusted all-cause mortality risk of incremental and frequent hemodialysis (HD) in the matched cohort (N = 50,756). Weighted coarsened exact matching were used based on age, sex, race, central venous catheter as vascular access, diabetes, and the Charlson Comorbidity Index. Model 1 is the unadjusted model. Model 2 includes Medicare as primary insurance, single pool Kt/V, body mass index, hemoglobin, albumin, corrected calcium, iron saturation, bicarbonate, log-transformed ferritin, and intact parathyroid hormone (iPTH). Model 3 includes variables in Model 2, a history of fluid overload, interdialytic weight gain, creatinine, phosphorus. Data on laboratories were extracted during the first 91 days of dialysis, and those except for ferritin and iPTH were further restricted to the initial thrice-weekly HD period before starting infrequent or frequent HD. CLurea, urea clearance.View Large Image Figure ViewerDownload (PPT) In prespecified subgroup analyses of the matched cohort comparing incremental HD with conventional HD, there was no statistical difference in all-cause mortality in subgroups of age, sex, race, central venous catheter use, or diabetic status. However, the incremental HD group showed a higher mortality risk among patients with a CCI ≥5 (HR 1.77, 95% CI 1.20–2.62). In the subgroup analyses comparing frequent HD with conventional HD, the mortality risk of frequent HD was consistently higher across all subgroups of age, sex, race, central venous catheter use, diabetic status, and higher comorbidity burden. However, in the lowest comorbidity risk category (CCI = 2), there was no statistical significant difference in mortality between frequent HD and conventional HD (HR 0.98, 95% CI 0.53–1.84) (Figure 4). Consistent results were found in the entire cohort (Supplementary Figures S2 and S3). This study compared survival among 50,162 conventional HD patients, 434 incremental HD patients, and 160 frequent HD patients who initiated HD treatment in a large US dialysis organization. After matching for key demographic and comorbid characteristics and comparison with the conventional HD group, overall mortality was not different in the incremental HD group but significantly higher in the frequent HD group. These results were robust across the adjustment models including a sensitivity analysis with adjustment for RKF. However, comorbidity burden modified the association between HD frequency and all-cause mortality; patients in the incremental HD group with greater comorbid burden (CCI ≥5) had a significantly higher risk of mortality. To date, there are no randomized, controlled trials examining the effect of incremental compared with conventional HD on mortality risk, and only a few observational studies have been conducted. Lin et al.19Lin X. Yan Y. Ni Z. et al.Clinical outcome of twice-weekly hemodialysis patients in shanghai.Blood Purif. 2012; 33: 66-72Crossref PubMed Scopus (55) Google Scholar reported a prospective observational study of 2572 Chinese patients undergoing maintenance HD. Multivariable adjusted patient survival was similar between the 2 groups. Given that the study cohort comprised prevalent HD patients and RKF was not measured, these findings have limited generalizability to incident HD patients who face a higher early mortality risk. Hanson et al.20Hanson J.A. Hulbert-Shearon T.E. Ojo A.O. et al.Prescription of twice-weekly hemodialysis in the USA.Am J Nephrol. 1999; 19: 625-633Crossref PubMed Scopus (73) Google Scholar reported outcomes of patients on twice-weekly HD compared with a conventional regimen. A total of 15,067 HD patients were studied, among whom 570 were treated with twice-weekly HD. RKF data were not collected during the study follow-up period. Twice-weekly HD was associated with a 24% lower mortality than conventional HD. However, in the subgroup of incident patients, there was no difference in mortality between the 2 and 3 times per week HD groups after adjustment for estimated glomerular filtration rate at the time of dialysis initiation. It is plausible that the observed survival advantage in twice-weekly HD may have been moderated by higher baseline RKF and longer preservation of RKF.21Obi Y, Rhee C, Mathew A, et al. Residual kidney function decline and mortality in incident hemodialysis patients. J Am Soc Nephrol, in press.Google Scholar A recent US-based study of 23,645 incident HD patients compared conventional with incremental HD regimens by matching based on baseline renal clearance of urea, urine volume, gender diabetes, and use of central venous catheters. In that study, patients on an incremental HD regimen had significantly more preservation of renal clearance of urea, and those with adequate baseline RKF (i.e., ≥3 ml/min per 1.73 m2) had no significant difference in mortality.16Obi Y. Streja E. Rhee C.M. et al.Incremental hemodialysis, residual kidney function, and mortality risk in incident dialysis patients: a cohort study.Am J Kidney Dis. 2016 Feb 9; ([e-pub ahead of print] http://dx.doi.org/10.1053/j.ajkd.2016.01.008, accessed May 10, 2016)Google Scholar In addition, a prospective study of 168 incident HD patients found that the percentage of patients with RKF loss was significantly lower in patients initiated on twice-weekly HD compared with those initiated on conventional thrice-weekly HD.15Zhang M. Wang M. Li H. et al.Association of Initial Twice-Weekly Hemodialysis Treatment with Preservation of Residual Kidney Function in ESRD Patients.Am J Nephrol. 2014; 40: 140-150Crossref PubMed Scopus (91) Google Scholar Similar to this available literature, our study examines associations between incident dialysis regimens and outcomes, and our findings suggest that twice-weekly HD, a less costly and more patient-amenable regimen, may have no significant difference in mortality compared with conventional HD in certain selected patient populations with low or moderate comorbid disease burden (CCI 10 ml/min per 1.73 m2, and 90% are HD patients.1Saran R. Li Y.
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