What Is Identified and Unknown About Twice-Weekly Hemodialysis
Blood Purif. Writer manuscript; accessible in PMC 2016 Nov 17.
Printed in last edited kind as:
The 2006 Kidney Illness Outcomes High quality Initiative tips recommend twice-weekly or incremental hemodialysis for sufferers with substantial residual kidney operate (RKF). Nonetheless, in most prosperous nations de novo and abrupt transition to thrice-weekly hemodialysis is routinely prescribed for all dialysis-naïve sufferers no matter their RKF. We assessment historic developments in hemodialysis remedy initiation and revisit twice-weekly hemodialysis as an individualized, incremental therapy particularly upon first transitioning to hemodialysis remedy.
Within the 1960’s, hemodialysis therapy was first supplied as a life-sustaining therapy within the type of lengthy periods (≥10 hours) administered each 5 to 7 days. Twice- after which thrice-weekly therapy regimens have been subsequently developed to stop uremic signs on a long-term foundation. The thrice-weekly routine has since turn into the ‘commonplace of care’ regardless of a scarcity of comparative research. Some scientific research have proven advantages of excessive hemodialysis dose by extra frequent or longer therapy instances primarily amongst sufferers with restricted or no RKF. Conversely, in chosen sufferers with increased ranges of RKF and significantly increased urine quantity, incremental or twice-weekly hemodialysis could protect RKF and vascular entry longer with out compromising scientific outcomes. Proposed standards for twice-weekly hemodialysis embody urine output >500 ml/day, restricted interdialytic weight achieve, smaller physique measurement relative to RKF, and favorable dietary standing, high quality of life, and comorbidity profile.
Incremental hemodialysis together with twice-weekly regimens could also be protected and cost-effective therapy regimens that present higher high quality of life for incident dialysis sufferers who’ve substantial RKF. These proposed standards could information incremental hemodialysis frequency and warrant future randomized managed trials.
Key phrases: Twice-weekly hemodialysis, Incremental dialysis, Individualized remedy, Residual kidney operate, Finish-stage renal illness, Well being-related high quality of life
Nearly a decade has handed because the 2006 Kidney Illness Outcomes High quality Initiative (KDOQI) tips advisable twice-weekly hemodialysis (HD) therapy regimens for sufferers with substantial residual kidney operate (RKF) . Nonetheless, on the subject of HD adequacy targets, it is just the ‘golden rule’ for 1.2 single-pool Kt/V for thrice-weekly regimens that has been remembered in most dialysis-therapy training circles. To that finish, thrice-weekly HD has continued to be considered the usual of care of HD therapy for sufferers with end-stage renal illness (ESRD) . Whereas thrice-weekly HD seems to be an applicable therapy for a lot of ESRD sufferers, they proceed to indicate markedly decreased health-related high quality of life (HRQoL) and survival . The price of HD therapy is inherently excessive, usually 100–300 USD per therapy in most industrialized nations; therefore it locations an infinite monetary burden on the healthcare system worldwide. Given the cumulative proof mentioned under, we imagine that it’s time to revisit the so-called taboo of twice-weekly HD, as an necessary type of individualized and incremental therapy for chosen sufferers with ESRD [4, 5], particularly upon their de novo transition to dialysis. exhibits standards not too long ago developed by worldwide consensus for evaluating the appropriateness of twice-weekly HD (see Kalantar-Zadeh et al.  for extra particulars).
|1. Urine output >0.5 liters/day|
|2. Interdialytic weight achieve <2.5 kg (or <5% of dry weight) at intervals of three–4 days|
|3. Restricted or readily manageable cardiovascular or pulmonary signs with out clinically vital fluid overload|
|4. Acceptable physique measurement relative to RKF|
|5. Rare or readily manageable hyperkalemia (Okay >5.5 mEq/l)|
|6. Rare or readily manageable hyperphosphatemia (P >5.5 mg/dl)|
|7. Good dietary standing with out overt hypercatabolic state|
|8. Acceptable responsiveness to anemia remedy with Hb >8 g/dl|
|9. Restricted or simply manageable comorbid circumstances|
|10. Passable health-related high quality of life|
Historic Modifications in HD Frequency
Traditionally and upon conception and institution of HD remedy, period and frequency of HD therapy was decided to stop uremic signs, akin to lethargy, pruritus, nausea, vomiting, quantity overload, and peripheral neuropathy. Within the early 1960’s, ESRD sufferers have been prescribed one lengthy HD session (20–24 hours in period) each 5 to 7 days . Given the insufficient therapy of uremia with such sporadic HD therapies and the distinctive severity of kidney failure amongst these sufferers who had little to no remaining residual kidney operate (RKF), the frequency of HD therapies was step by step elevated over time, concurrent with enchancment in HD methods and techniques. By the late 1960’s, the twice-weekly schedule was employed in lots of applications (), however a excessive prevalence of uremic neuropathy was nonetheless noticed . Throughout congressional discussions surrounding the Medicare ESRD Program legislature in 1973, the thrice-weekly schedule was thought to supply a extra useful HD routine and was thought-about ‘the very best compromise’ to ship HD therapy to as many sufferers as potential with the restricted sources accessible . Previous to this, HD was actually a life-sustaining intervention in solely chosen ESRD sufferers, and only a few diabetic or aged sufferers have been accepted for therapy.
Since then, there was speedy and progressive progress in HD methods, tools, and practices, together with absolutely computerized HD machines, higher bio-compatibility and efficiency of dialysis membranes, increased purity of dialysate, and extra frequent creation and better longevity of arteriovenous fistulas. These advances have made HD therapies extra streamlined, environment friendly, and less expensive, permitting for an growth of sufferers who’re eligible for HD therapy, together with those that are aged and/or have a number of comorbidi-ties requiring earlier transition to dialysis whereas nonetheless having substantial RKF. Certainly, in 2012, greater than 40% of ESRD sufferers who began HD have been diabetic, and greater than 50% have been aged ≥65 years in each the US and Japan [8, 9]. Remedy time to attain focused solute clearance was additionally decreased over time . Worldwide knowledge has proven that over the interval of 1999 to 2011, imply therapy time was roughly 220 and 240 minutes within the US and Japan, respectively . These adjustments together with the thrice-weekly HD schedule enabled dialysis amenities to supply two alternating every-other-day schedules (Monday-Wednesday-Friday or Tuesday-Thursday-Saturday) throughout ≥3 shifts per day, leaving Sunday because the common ‘day-off’ for each sufferers and dialysis employees . Nonetheless, in some international locations such because the UK, there are dialysis facilities that additionally supply Sunday schedules .
Conflicting Outcomes from Medical Trials Evaluating HD Adequacy: Impact Modification by Residual Kidney Operate
As HD therapy turned established and broadly accessible, the objectives of caring for ESRD sufferers shifted from a spotlight upon rising short-term survival in direction of enhancing long-term outcomes. There was sturdy perception that better solute clearance ought to result in higher survival. This notion was additional strengthened by the 1981 Nationwide Cooperative Dialysis Research (NCDS) which confirmed that sustaining decrease time-averaged blood urea nitrogen concentrations decreases therapy withdrawals and hospitalizations . Though the HEMO Research did not show this idea through the use of increased HD dose or high-flux membranes , the Frequent Hemodialysis Community (FHN) Each day Trial reported considerably favorable results of 6-times-per-week in-center HD largely upon adjustments in left ventricular mass and bodily well being composite rating, as in contrast with standard thrice-weekly HD . The FHN Nocturnal Trial confirmed comparable developments , however the prolonged follow-up research discovered increased mortality in sufferers randomly assigned to frequent nocturnal HD .
Though these outcomes could appear conflicting, the useful results of excessive HD dose or frequency in a few of these research are probably noticed in sufferers with little or no RKF. The NCDS trial restricted contributors to those that had creatinine clearances <3 ml/min , but in contemporary practice, patients are typically transitioned to HD when kidney function is above this threshold. A subgroup analysis of the HEMO study suggested that patients with longer dialysis vintage (≥3.7 years), most of whom were presumed to have little RKF, may benefit from receipt of the high-flux dialysis membrane . In the FHN Daily Trial, 84% of patients had dialysis vintages ≥2 years, and 66% were anuric . In contrast, in the FHN Nocturnal Trial where higher mortality was observed in the frequent nocturnal HD group, patients had a comparatively lower median dialysis vintage of approximately 1 year, and 47% of patients had urine volume >500 ml/day . It is very important observe that within the latter research, sufferers who obtained extra frequent HD had considerably quicker lack of their RKF . This unfavorable consequence has been highlighted in commentaries by Daugirdas et al. , Kalantar-Zadeh et al. [3, 4], Rhee et al. , and Wong et al. . The Initiating Dialysis Early and Late (IDEAL) research additionally confirmed comparable outcomes, such that earlier initiation of HD didn’t enhance survival nor main scientific outcomes , suggesting that HD therapy presents little profit to sufferers with substantial RKF.
The clearance of plasma molecules by HD is partially dependent upon molecular measurement relative to membrane pore measurement. Subsequently, the anticipated advantage of HD therapy ought to be weighed towards potential opposed results on a case-by-case foundation as mentioned under (). The steadiness between the advantages and harms of HD therapy could also be influenced by a number of elements akin to life expectancy, dietary consumption (i.e., protein, sodium, potassium, and phosphorus), treatment adherence, entry to medical sources, and, most significantly, RKF.
Potential Advantages of Twice-Weekly HD
We argue that twice-weekly HD within the present period shouldn’t be a suboptimal therapy routine for sufferers with substantial RKF as in contrast with standard thrice-weekly HD. Utilizing the equation for traditional Kt/Vurea by Daugirdas et al. , urea clearances in thrice-weekly HD versus twice-weekly HD therapy regimens with 1.2 single-pool Kt/V and 210-minute therapy instances are equal to 9.3 ml/min versus 6.15 m/min, respectively. This differential in urea clearance is just like the minimal threshold RKF degree of three.0 ml/min at which twice-weekly HD is advisable by the KDOQI tips . This main differential in clearance bears substantial scientific significance, and it’s uncertain that different interventions (akin to rising HD dose per session, enhancing dietary administration, and use of medication together with erythropoiesis-stimulating brokers, phosphate binders, and calcimimetics) supply the identical diploma of profit as preservation of RKF. Provided that over 100,000 sufferers provoke HD yearly within the US, amongst whom 45% have estimated glomerular filtration charges ≥10 ml/min/1.73 m 2 upon dialysis initiation , applicable implementation of twice-weekly HD could have a good impression upon ESRD affected person outcomes in addition to appreciable financial benefits. At the moment accessible proof for much less frequent HD is summarized in .
|Research Writer (Journal, 12 months)||Cohort description||Publicity (vs. thrice-weekly HD)||Outcomes|
|Mortality Hanson et al.  (Am J Nephrol 1999)||Incident HD (n = 4,888)
Prevalent HD (n = 10,179)
|Twice-weekly HD||Decrease adjusted mortality danger in each incident and prevalent HD sufferers. This affiliation was attenuated after adjustment for RKF at HD initiation (accessible solely in incident sufferers).|
|Lin et al.  (Blood Purif 2012)||Incident HD (n = 639)
Prevalent HD (n = 673)
|Twice-weekly HD||Comparable adjusted mortality danger total in addition to subgroups of incident and prevalent sufferers (RKF knowledge not accessible).|
|Stankuviene et al.  (Medicina 2010)||Incident HD (n = 2,428)||As soon as- and twice-weekly HD||Larger adjusted mortality (RKF knowledge not accessible)|
|Elamin and Abu-Aisha  (Arab J Nephrol Transplant 2012)||Prevalent HD (n = 2,012)||Twice-weekly HD||Larger 1-year crude mortality (85% vs. 89%)|
|Fernandez-Lucas et al.  (Nephrologia 2012)||Incident HD (n = 95)||Incremental HD||Higher crude survival|
|Residual renal operate Lin et al.  (Nephrology 2009)||Prevalent HD (n = 74)||Twice-weekly HD||Higher RKF preservation (with out adjustment)|
|Fernandez-Lucas et al.  (Nephrologia 2012)||Incident HD (n = 95)||Twice-weekly HD||Higher RKF preservation (with out adjustment)|
|Caria et al.  (BMC Nephrology 2014)||Incident HD (n = 68)||As soon as-weekly HD with low protein weight loss program||Higher RKF preservation (with out adjustment)|
|Zhang et al.  (Am J Nephrol 2014)||Incident HD (n = 85)||Twice-weekly HD||Higher RKF preservation (with out adjustment) Odds ratio for quicker RKF loss was 7.2 after adjustment for intercourse, urea discount price, and intradialytic hypotension episode.|
|Dietary parameters Supasyndh et al.  (J Med Assoc Thai 2009)||Prevalent HD (n = 142)||Twice-weekly HD||Comparable dietary laboratory parameters and protein consumption, however better power consumption|
|Lin et al.  (Nephrology 2009)||Prevalent HD (n = 74)||Twice-weekly HD||Comparable dietary laboratory parameters|
Preservation of RKF
RKF in dialysis sufferers performs necessary roles in fluid and salt removing, efficient phosphorus excretion, middle-molecule clearance, and endogenous vitamin D and erythropoietin manufacturing [2–4]. It has additionally been related to increased HRQoL, decrease irritation, diminished left ventricular hypertrophy, and higher survival. Nonetheless, RKF decline is quicker in sufferers receiving thrice-weekly HD remedy than in these receiving peritoneal dialysis  ; whereas HD per se could speed up RKF decline by episodic ischemic insults to the kidney, provision of much less frequent HD could mitigate this potential danger of HD. Certainly, in line with the outcomes from the FHN research that confirmed quicker lack of RKF in frequent nocturnal HD in contrast with standard thrice-weekly HD , a number of non-controlled scientific research indicated that twice-weekly HD could protect RKF [22–24]. In a research of 85 incident HD sufferers in Shanghai initiated on both a twice-weekly or thrice-weekly HD routine, a better proportion of sufferers receiving twice-weekly HD had preservation of RKF in the course of the first yr of HD initiation . There are complementary research suggesting that dialysis dose didn’t have a big impression on outcomes in sufferers with sure ranges of RKF [25, 26], supporting the notion that twice-weekly HD for such sufferers could also be an applicable selection.
Survival and HD Frequency
In a retrospective research cohort performed by the US Renal Information System within the late Nineteen Nineties, 6.1% and a pair of.7% of the sufferers underwent twice-weekly HD therapy regimens in 4,888 incident and 10,179 prevalent HD sufferers, respectively . Elements related to twice-weekly HD schedules included older age, feminine gender, white race, shorter dialysis classic, increased serum albumin, decrease serum creatinine, decrease physique mass index, and better baseline RKF on the time of HD initiation. After adjustment for demographics, explanation for ESRD, comorbid circumstances, and dietary standing, twice-weekly HD regimens confirmed 21% and 24% decrease mortality danger in incident and prevalent HD sufferers, respectively, versus thrice-weekly HD. This survival differential was attenuated upon adjustment for baseline RKF, which was accessible solely in incident HD sufferers. There are two extra research that additionally reported higher survival amongst sufferers who obtained twice-weekly HD with out adjustment for RKF [23, 28]. None of those research have examined the extent of RKF the place sufferers may benefit from twice-weekly HD.
Different Potential Advantages
Having twice-weekly HD periods can even end in much less frequent arteriovenous fistula or graft cannulations, which can extend the longevity of dialysis vascular entry . The FHN research has proven that in contrast with standard HD, extra frequent HD was related to increased danger of vascular problems together with restore, loss, or vascular entry associated hospitalization; this was thought to extra probably be a consequence of elevated HD frequency than heightened surveillance . Moreover, by having one much less HD therapy per week, sufferers can spend extra time participating in actions exterior of the dialysis unit, which can result in considerably higher high quality of life [2–4]. Satirically, sure populations akin to sufferers who’re aged, have superior most cancers, or produce other extreme comorbid circumstances are much less prone to profit from extra frequent dialysis, and fewer frequent HD with conservative administration could also be thought-about as a palliative choice even when such sufferers have restricted RKF.
Potential Disadvantages of Twice-Weekly HD
Interdialytic Weight Achieve and Ultrafiltration
A number of research have recognized the lengthy (2-day) interdialytic interval as an impartial danger issue for all-cause mortality and cardiovascular hospitalization in sufferers handled with thrice-weekly HD [30–32], probably as a result of fluid overload and/or electrolyte derangements. Though the potential problems of the lengthy interval could appear to counteract the advantages of twice-weekly HD, opposed outcomes related to the lengthy interdialytic interval weren’t noticed amongst incident HD sufferers , a lot of whom probably have the next RKF than prevalent sufferers and thus maintained higher electrolyte and fluid steadiness. Furthermore, it’s potential that the upper mortality of the lengthy interdialytic interval pertains to extra dialysis and abrupt removing and shifts of fluid and electrolyte (e.g., potassium) .
There could also be misconceptions that bigger interdialytic weight features (IDWG) will probably be noticed with twice-weekly HD schedules in contrast with thrice-weekly schedules, and that aggressive ultrafiltration could also be required to take away extra fluid collected in the course of the interdialytic HD interval. Whereas massive IDWGs could promote left ventricular hypertrophy and congestive coronary heart failure by rising afterload and myocardial oxygen demand , this shouldn’t be the case in sufferers with substantial RKF who’re compliant with restriction of fluid consumption. Certainly, it’s believable that extra frequent HD could result in better IDWGs and cardiac structural abnormalities over time as a result of quicker lack of RKF . Speedy ultrafiltration charges might also contribute to intradialytic hypotension, subclinical cardiac gorgeous, and myocardial ischemia . Higher IDWG (≥5% of dry weight) and better ultrafiltration charges (≥10 ml/h/kg) are related to increased danger of mortality [35, 36], and sufferers with superior coronary heart illness could require longer or extra frequent HD therapies . Aggressive ultrafiltration usually causes cramping, dizziness, and fatigue that makes dialysis insupportable. Different potential unfavorable options of twice-weekly HD that bear point out embody persistent azotemia and electrolyte disturbances (e.g., hyperkalemia, hypercalcemia, and hyperphosphatemia), however these problems are much less prone to happen in sufferers with substantial RKF who’re the optimum candidates for twice-weekly HD .
Dietary Standing and Dietary Consumption
Whereas thrice-weekly HD sufferers are advisable to have excessive dietary protein consumption (1.2–1.3 g/kg/day), which is in sharp contradistinction to non-dialysis CKD sufferers who’re prescribed low protein diets (0.6–0.7 g/kg/day), there isn’t any identified dietary advice for sufferers on twice-weekly remedy with substantial RKF. Dietary consumption might also seem to have an effect on the superb steadiness of HD frequency in conflicting methods, as sufferers with intact urge for food normally have good dietary standing, whereas their serum concentrations of urea nitrogen, potassium, and phosphorus are usually excessive.
Caria et al.  from Italy has not too long ago recommended that rare HD regimens of once-weekly HD, complemented by very low protein, low phosphorus diets supplemented with ketoacids had favorable impression on preserving sufferers’ urine output. We at the moment suggest a dietary protein consumption of 0.8–1.0 g/kg/day to most twice-weekly HD with substantial RKF, whereas on non-dialysis days the dietary protein consumption could also be comparatively decrease.
Incremental transition from twice-weekly to thrice-weekly HD could also be ultimately thought-about when enhance in dialysis dose fails to compensate for decreased RKF. Nonetheless, RKF decline charges differ throughout HD sufferers, and with out common evaluation of sufferers’ RKF and urine output, the suitable juncture for rising HD frequency could also be ignored or missed. As this time, there may be little proof as to which sufferers prescribed twice-weekly HD could proceed to profit from this therapy routine over time, versus require transition to extra frequent HD regimens. It might even be difficult to persuade sufferers who’re accustomed to the twice-weekly HD routine to extend their dialysis time and/or frequency, which can be inevitable if their RKF declines over time. We really feel that the factors set forth by worldwide consensus (see ) is a superb device to routinely assess the necessity for such transitions and to speak with sufferers when the suitable time arrives.
Incident dialysis sufferers with substantial RKF (e.g., KRU >3.0 ml/min/1.73 m2 ) are probably good candidates for twice-weekly HD, whereas these with little or no RKF could profit from standard thrice-weekly or much more frequent HD, relying on different elements together with age, comorbid circumstances, and dietary consumption. Twice-weekly HD schedules could play an necessary position as the primary routine for sufferers incrementally initiating HD, and in addition as a palliative method for conservative administration in sure populations with the intention to optimize HRQoL and useful resource utilization. Nonetheless, implementation twice-weekly HD has been hindered by a paucity of proof of its related outcomes (advantages and dangers). To that finish the normal view of nephrology communities in prosperous nations has been that twice-weekly HD is an inferior choice and a dialogue taboo; nonetheless there has very not too long ago been a surge of provocative literature resulting in its reconsideration [2–5]. The not too long ago developed consensus standards for implementing twice-weekly HD is a vital growth in selling the idea of individualized incremental HD regimens, they usually should be validated and refined in future analysis research.
Conflicts of Curiosity
KKZ has obtained honoraria and/or assist from Abbott, Abbvie, Alexion, Amgen, American Society of Nephrology, Astra-Zeneca, Aveo, Chugai, DaVita, Fresenius, Genetech, Haymarket Media, Hospira, Kabi, Keryx, NIH, Nationwide Kidney Basis, Relypsa, Resverlogix, Sanofi, Shire, Vifor, and ZS-Pharma.