Outcomes from the Dialysis Outcomes and Observe Patterns Examine
Sudden loss of life is a number one reason for loss of life in sufferers on upkeep hemodialysis (HD). Throughout HD classes, the gradient between serum and dialysate ranges leads to fast electrolytes shifts, which can contribute to arrhythmias and sudden loss of life. Controversies exist on the optimum electrolyte focus within the dialysate; particularly, it’s unclear whether or not affected person outcomes differ amongst these handled with dialysate potassium (DK) focus of three mEq/L in comparison with 2 mEq/L.
Potential cohort examine
Setting & Individuals
55,183 sufferers from 20 nations within the Dialysis Outcomes and Observe Patterns Examine phases 1–5 (1996–2015).
DK at examine entry.
Cox regression was used to estimate the affiliation between DK and each all-cause mortality and an arrhythmia composite end result (arrhythmia-related hospitalization or sudden loss of life), adjusting for potential confounders.
Throughout a median follow-up of 16.5 months, 24% of sufferers died and seven% had an arrhythmia composite end result. No significant distinction in medical outcomes had been noticed for sufferers handled with DK 3 vs. 2 mEq/L; the adjusted hazard ratio (95% CI) was 0.96 (0.91, 1.01) for mortality and 0.98 (0.88, 1.08) for the arrhythmia composite. Outcomes had been comparable throughout pre-dialysis serum potassium (SK) ranges. As in prior research, increased SK was related to adversarial outcomes. Nevertheless, DK solely had minimal impression on SK measured pre-dialysis (+0.09 mEq/L SK per 1 mEq/L DK; 95% CI: 0.05, 0.14).
Knowledge weren’t out there on delivered (vs. prescribed) DK and post-dialysis SK; doable unmeasured confounding.
Together, these outcomes counsel that approaches apart from altering DK focus (e.g., schooling on dietary Okay sources, prescription of Okay-binding drugs) could advantage additional consideration to cut back dangers related to excessive SK.
Index phrases: dialysate potassium, hemodialysis, hyperkalemia, mortality, serum potassium
Sudden loss of life is a number one reason for loss of life in sufferers requiring hemodialysis (HD), with 27% of all deaths attributable to arrhythmic mechanisms.1 In thrice weekly upkeep HD, these occasions are likely to cluster within the interval simply previous to the primary dialysis session of the week, when fluid overload and the extent of assorted uremic toxins are highest, and within the interval throughout and instantly following HD classes.2–4 Whereas a multiplicity of things contribute to sudden loss of life, it’s speculated that the elevated threat throughout and instantly following the HD session is related to massive fluid and electrolyte shifts that happen throughout this time.3
Hyperkalemia is frequent in sufferers with kidney failure as a consequence of diminished renal potassium excretion inflicting disturbances in coronary heart rhythm and cardiac arrest in excessive instances.5,6 Excessive pre-dialysis serum potassium (SK) is acknowledged as a threat issue for sudden loss of life and all-cause mortality in HD sufferers.7,8 Potassium has the potential to maneuver freely throughout the dialyzer membrane throughout the HD session, usually being transferred from a affected person’s blood into the dialysate.9 The dialysate potassium (DK) focus is a modifiable issue that may alter SK concentrations all through the HD session and thus probably impacts the chance for arrhythmias and cardiac arrest. 10 Outcomes of research inspecting DK results on sudden loss of life and all-cause mortality have been blended. Kovesdy et al.7 suggested that hyperkalemic sufferers with a decrease DK tub could have higher survival, whereas two massive case-control research investigated sudden loss of life occasions occurring throughout dialysis and concluded there was an elevated threat of sudden loss of life for sufferers dialyzing with DK=1 and even DK=0.11,12 Whereas no suggestion on DK ranges has been supplied within the Kidney Illness Outcomes High quality Initiative (KDOQI) heart problems tips,13 a number of current critiques are in settlement that DK < 2 mEq/L ought to be averted, significantly in sufferers with excessive pre-dialysis potassium, to keep away from a fast lower in plasma potassium.6,14–18 Accordingly, anecdotal studies point out that using DK < 2 mEq/L has grow to be more and more uncommon. This prompted us to research whether or not DK = 2 mEq/L was nonetheless too low, compared to the next DK of three mEq/L.
Within the absence of conclusive outcomes, many clinicians’ DK prescription typically goals to maintain SK inside an “acceptable” vary. Some nephrologists make selections qualitatively primarily based on medical judgment and expertise, others anecdotally use the “rule of seven” and prescribe DK to make the sum of DK and pre-dialysis SK roughly seven,19 whereas some services’ medical workers elect to supply a uniform DK to all sufferers. Nevertheless, optimum prescription practices stay unknown: treating with decrease DK promotes better intradialytic Okay flux and will increase the chance of hypokalemia; conversely, treating with the next DK could predispose sufferers to hyperkalemia. The previous could also be worsened amongst sufferers with already low pre-dialysis SK and the latter amongst sufferers with excessive pre-dialysis SK. Additional, treating excessive pre-dialysis SK sufferers with a low DK could trigger a fast intradialytic shift in potassium throughout the first hour of dialysis. Thus, there may be cause to invest that the impact of DK could also be modified primarily based on sufferers’ pre-dialysis SK.
A earlier Dialysis Outcomes and Observe Patterns Examine (DOPPS) evaluation20 noticed associations between sudden loss of life and numerous modifiable practices: low therapy time, low Kt/V, excessive ultrafiltration quantity, and low DK. Given newer traits in the direction of increased DK and the dearth of clear proof throughout research evaluating the 2 mostly used DK prescriptions (2 vs. 3 mEq/L), we revisited the difficulty of DK and medical outcomes utilizing a bigger and extra up to date cohort of sufferers. On this examine, we leveraged information from the worldwide cohort of in-center HD sufferers within the DOPPS to evaluate the dangers of various DK prescriptions general and amongst sufferers with totally different SK ranges. We additionally examined the associations between pre-dialysis SK ranges and outcomes in addition to the affiliation between DK and SK.
The DOPPS (http://www.dopps.org) is a world potential cohort examine of sufferers age 18 or older handled with in-center HD. The examine is designed to watch sufferers over time and correlate practices and outcomes in numerous medical settings all over the world to assist researchers and clinicians determine greatest practices and different modifiable traits that enhance dialysis affected person lives. Sufferers had been randomly chosen from nationwide samples of dialysis services inside every nation.21,22 On this evaluation, information from members within the DOPPS part 1 (1996–2001), part 2 (2002–2004), part 3 (2005–2008), part 4 (2009–2011), and part 5 (2012–2015) had been used. Collaborating nations included France, Germany, Italy, Japan, Spain, United Kingdom, and the US in phases 1–5, Australia and New Zealand (ANZ), Belgium, Canada, and Sweden in phases 2–5, and the Gulf Cooperation Council (GCC, together with Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates), China, Russia, and Turkey in part 5. US Examine approval was obtained by a central Institutional Evaluate Board (examine quantity 98004-19). Extra examine approval and affected person consent had been obtained as required by nationwide and native ethics committee laws.
Knowledge on demographics, comorbid situations, laboratory values (single most up-to-date worth), and prescriptions had been abstracted from medical information utilizing uniform and standardized information assortment instruments. Mortality and hospitalization occasions and the first causes of those occasions had been collected throughout examine follow-up. Sufferers with pre-dialysis SK and DK information out there at DOPPS entry (baseline: single most up-to-date worth at examine entry) had been eligible for this evaluation. Sufferers in Japan had been excluded from analyses of medical outcomes as a consequence of lack of variation within the major publicity variable (DK=2 mEq/L in all sufferers), however had been included in descriptive figures for instance the within- and across-country variation. See for eligibility standards particulars.
To estimate the affiliation between baseline pre-dialysis SK and all-cause mortality, we used Cox regression stratified by DOPPS part and nation, and by US massive dialysis group when relevant. Proportional hazards had been confirmed by examination of log-log survival plots and by testing the interplay between log-time and the publicity of curiosity. We accounted for facility clustering utilizing strong sandwich covariance estimators. We categorized SK, with 4.0–5.0 mEq/L (50% of sufferers) because the reference group. Fashions had been analyzed each unadjusted and adjusted for the next baseline covariates: age, intercourse, classic, the 13 comorbid situations listed in , vascular entry, physique mass index (BMI), nPCR, serum albumin, calcium, bicarbonate, phosphorus (linear and quadratic time period to account for U-shaped affiliation), dialysate bicarbonate, hemoglobin, therapy time, and Kt/V. Time in danger began at examine enrollment and ended on the time of loss of life, seven days after leaving the ability as a consequence of switch or change in kidney alternative remedy modality, loss to follow-up, transplantation, or finish of examine part (whichever occasion occurred first). The secondary examine end result was an arrhythmia composite outlined as time to the primary of any of the next occasions: loss of life as a consequence of both hyperkalemia, hypokalemia, cardiac arrhythmia, or cardiac arrest (trigger unknown), or inpatient hospitalization as a consequence of atrial fibrillation or different arrhythmia, or a process for cardioversion, AICD (defibrillator) or pacemaker placement. We excluded from analyses of the composite end result services missing info on causes of loss of life and hospitalization.
|Serum Okay (mEq/L)|
|< 4.0||4.0 – 5.0||5.1 – 6.0||> 6.0|
|N sufferers (%)||6300 (11%)||27525 (50%)||16959 (31%)||4399 (8%)|
|Age (years)||63.8 ± 15.2||63.0 ± 15.2||61.8 ± 15.3||60.4 ± 15.3|
|Intercourse (% males)||56%||58%||59%||56%|
|Black race (%)||20%||17%||11%||7%|
|Classic (years)||2.0 ± 3.7||2.9 ± 4.4||4.0 ± 5.2||4.5 ± 5.4|
|Central venous catheter use (%)||47%||34%||26%||25%|
|Single Pool Kt/V||1.41 ± 0.35||1.46 ± 0.34||1.46 ± 0.33||1.44 ± 0.34|
|Remedy time (min)||219 ± 37||225 ± 38||230 ± 39||233 ± 39|
|Dialysate Potassium (mEq/L)||2.4 ± 0.7||2.2 ± 0.6||2.1 ± 0.6||2.0 ± 0.6|
|Laboratory and biometric measurements|
|Physique mass index (kg/m2)||26.6 ± 6.4||26.6 ± 6.3||26.0 ± 6.0||25.2 ± 5.5|
|Pre-dialysis SBP (mm Hg)||144 ± 24||145 ± 23||145 ± 23||145 ± 23|
|Hemoglobin (g/dL)||10.7 ± 1.6||11.0 ± 1.5||11.2 ± 1.6||11.2 ± 1.7|
|Normalized PCR (g/kg/day)||0.85 ± 0.24||0.95 ± 0.25||1.04 ± 0.26||1.10 ± 0.27|
|Serum Creatinine (mg/dL)||6.6 ± 2.8||7.7 ± 3.0||8.9 ± 2.9||9.7 ± 3.0|
|Serum Albumin (g/dL)||3.46 ± 0.61||3.65 ± 0.53||3.76 ± 0.51||3.81 ± 0.52|
|WBC depend (103 cells/mm3)||7.6 ± 2.9||7.3 ± 2.5||7.2 ± 2.4||7.4 ± 2.5|
|Serum Bicarbonate (mEq/L)||23.9 ± 4.0||22.9 ± 3.6||22.1 ± 3.6||21.3 ± 3.8|
|Serum Calcium (mg/dL)||8.8 ± 0.9||9.0 ± 0.9||9.1 ± 0.9||9.2 ± 0.9|
|Serum Phosphorus (mg/dL)||4.7 ± 1.7||5.2 ± 1.7||5.6 ± 1.8||6.0 ± 2.0|
|Serum Potassium (mEq/L)||3.6 ± 0.3||4.5 ± 0.3||5.5 ± 0.3||6.5 ± 0.4|
|Comorbid situations (%)|
|Coronary artery illness||43%||42%||41%||38%|
|Most cancers (non-skin)||13%||13%||12%||11%|
|Different heart problems||31%||30%||32%||31%|
|Coronary heart failure||36%||33%||32%||30%|
|Peripheral vascular illness||27%||26%||26%||25%|
|Recurrent cellulitis, gangrene||9%||9%||9%||9%|
Equally, we used Cox regression to estimate the associations of baseline DK with all-cause mortality and the arrhythmia composite end result, each unadjusted and adjusted as above. DK was categorized into three teams, with 2.0–2.5 mEq/L because the reference. We additionally estimated the impact of DK as a steady variable utilizing instrumental variable analyses, carried out as described beneath, however modified to make use of a Cox mannequin within the second stage. We then assessed whether or not the affiliation between DK and medical outcomes was modified by degree of pre-dialysis SK. As a result of DK=2.0 and DK=3.0 mEq/L are by far the most typical prescriptions in use, we restricted this comparability to sufferers with both DK=2.0 (reference) or 3.0 mEq/L and examined the affiliation amongst 4 subgroups of sufferers primarily based on pre-dialysis SK degree.
To evaluate the affiliation between DK and pre-dialysis SK, we first modeled SK as the end result variable in a linear blended mannequin to account for facility clustering, treating DK as a steady publicity variable. We modeled the connection adjusting for DOPPS part and nation solely, and subsequently adjusting as above. As a result of we suspected a big diploma of confounding by indication (i.e., sufferers with decrease pre-dialysis SK being individualized to obtain the next DK), we carried out an instrumental variable two-stage least squares (2SLS) evaluation to account for this bias. Whereas violations of different assumptions of instrumental variable analyses can’t be formally assessed, we demonstrated the energy of the DOPPS facility because the instrument23: F = 13.6. Moreover, we noticed higher steadiness throughout affected person traits by quartile of facility imply DK than by affected person DK (Desk S2). Whereas utilizing facility because the instrument will be an efficient technique to handle unmeasured patient-level confounding, group-level confounding will also be a priority.24 We thus moreover adjusted for six dialysis unit practices: the proportion of sufferers in a facility with a catheter, with spKt/V < 1.2, with albumin < 3.5 g/dL, and with phosphorus ≥ 5.5 mg/dL, and imply within-facility ranges of hemoglobin and dialysate bicarbonate. As a result of Okay-binding resins are additionally probably prescribed on the premise of SK, we handled Okay resins as an extra endogenous variable to concurrently account for the confounding by indication attributable to DK and potassium-binding resin use.25 To check the robustness of the instrumental variable findings, sensitivity analyses had been carried out utilizing linear blended fashions with: (1) crude facility imply DK because the publicity, and (2) proscribing to services prescribing a uniform DK to ≥ 90% of sufferers, a method much like that employed by Hecking et al. for dialysate sodium research.26
We assumed the info had been lacking at random; lacking covariate values had been addressed by a number of imputation utilizing the chained equation technique by IVEware.27,28 Lacking values had been sequentially up to date utilizing the bootstrap or Markov Chain Monte Carlo technique, primarily based on a number of regression fashions with different variables as covariates. This process was carried out for 10 cycles, thereby developing an imputed information set. Outcomes from 5 such imputed information units had been mixed for the ultimate evaluation utilizing Rubin’s components.29 Largely because of the excessive variety of mannequin covariates, 67% of sufferers had been lacking information for a minimum of one adjustment covariate. The proportion of lacking information was beneath 10% for all variables used for covariate adjustment, except for nPCR (35%), Kt/V (32%), serum bicarbonate (22%), and dialysate bicarbonate (18%). All analyses had been carried out utilizing SAS software program, model 9.4 (SAS institute, Cary, NC).
Pre-dialysis serum Okay ranges
The distribution of SK, by nation, in DOPPS part 5 is proven in . Imply SK was highest in Russia (5.3 mEq/L) and lowest in america (US) (4.6 mEq/L). Development analyses () demonstrated that SK has decreased over the previous 20 years in Europe, Australia, New Zealand (Europe/ANZ) and Japan. In North America, imply SK remained pretty fixed. In every nation, SK ranges collected on the first HD session of the week (Monday/Tuesday) had been barely increased than ranges collected midweek (Wednesday/Thursday); the distinction ranged from 0.01 mEq/L in China to 0.19 mEq/L in Germany.
Dialysate Okay prescription
reveals DK prescription patterns in every DOPPS nation throughout part 5 (2012–15). DK of two.0–2.5 mEq/L was the most typical prescription worldwide, prescribed to 75% of sufferers within the US and >99% of sufferers in Japan. DK was highest in Germany, the place DK of three.0 mEq/L or better was utilized in 75% of sufferers. Prescription of DK of 1.0–1.5 mEq/L was primarily concentrated in Spain. The apply sample of prescribing a uniform DK to ≥ 90% of sufferers within the facility diversified broadly throughout nations (desk insert beneath ). Along with Japan, uniform DK prescription of two.0 mEq/L was frequent in China (84% of services) and Turkey (79%). In distinction, uniform DK prescription was much less frequent within the US (27% of services) and barely utilized in Germany (5%) and Canada (5%). The development analyses () present that DK has been steadily growing in Europe/ANZ throughout the DOPPS phases. In North America, current traits present a decline within the proportion of sufferers prescribed DK < 2 mEq/L, down to five% in part 5.
Examine pattern traits
Descriptive affected person traits, by SK and DK classes, are proven in and . Sufferers within the lowest SK group differed from sufferers within the highest SK group in some ways; as an illustration they had been older, had shorter dialysis classic, extra catheter use, decrease normalized protein catabolic charge (nPCR), and decrease creatinine, albumin, and phosphorus concentrations. Affected person traits additionally differed throughout DK prescriptions; as an illustration, these within the highest DK group had been older, had shorter dialysis classic, extra catheter use, decrease nPCR, decrease creatinine and albumin concentrations, decrease SK, and had been extra prone to have been prescribed a diuretic.
|All||Dialysate Okay (mEq/L)|
|1.0 – 1.5||2.0 – 2.5||3.0 – 4.0|
|N sufferers (%)||55183||8109 (15%)||33497 (61%)||13577 (25%)|
|Age (years)||62.5 ± 15.3||61.4 ± 15.4||61.6 ± 15.4||65.5 ± 14.5|
|Intercourse (% males)||58%||60%||58%||56%|
|Black race (%)||15%||6%||18%||11%|
|Classic (years)||3.3 ± 4.7||4.3 ± 5.5||3.5 ± 4.8||2.1 ± 3.7|
|Central venous catheter use (%)||32%||26%||30%||41%|
|Single Pool Kt/V||1.45 ± 0.34||1.46 ± 0.33||1.46 ± 0.33||1.42 ± 0.35|
|Remedy time (min)||226 ± 39||227 ± 39||227 ± 37||225 ± 43|
|Dialysate Potassium (mEq/L)||2.2 ± 0.6||1.3 ± 0.3||2.0 ± 0.1||3.1 ± 0.3|
|Laboratory and biometric measurements|
|Physique mass index (kg/m2)||26.3 ± 6.2||25.5 ± 5.5||26.4 ± 6.3||26.6 ± 6.1|
|Pre-dialysis SBP (mm Hg)||145 ± 23||144 ± 23||146 ± 23||142 ± 23|
|Hemoglobin (g/dL)||11.1 ± 1.6||11.3 ± 1.6||11.0 ± 1.6||10.9 ± 1.6|
|Normalized PCR (g/kg/day)||0.98 ± 0.26||1.07 ± 0.26||0.98 ± 0.26||0.91 ± 0.25|
|Serum Creatinine (mg/dL)||8.1 ± 3.1||8.7 ± 2.9||8.5 ± 3.1||6.9 ± 2.8|
|Serum Albumin (g/dL)||3.68 ± 0.54||3.74 ± 0.51||3.69 ± 0.53||3.59 ± 0.58|
|WBC depend (103 cells/mm3)||7.3 ± 2.5||7.2 ± 2.4||7.3 ± 2.6||7.4 ± 2.6|
|Serum Bicarbonate (mEq/L)||22.7 ± 3.7||22.7 ± 3.5||22.7 ± 3.7||22.8 ± 3.8|
|Serum Calcium (mg/dL)||9.0 ± 0.9||9.2 ± 0.9||9.0 ± 0.9||8.9 ± 0.9|
|Serum Phosphorus (mg/dL)||5.3 ± 1.8||5.4 ± 1.8||5.4 ± 1.8||5.1 ± 1.7|
|Serum Potassium (mEq/L)||4.9 ± 0.8||5.1 ± 0.8||4.9 ± 0.8||4.7 ± 0.8|
|Comorbid situations (%)|
|Coronary artery illness||42%||39%||41%||46%|
|Most cancers (non-skin)||12%||12%||12%||15%|
|Different heart problems||31%||33%||28%||35%|
|Coronary heart failure||33%||31%||33%||33%|
|Peripheral vascular illness||26%||27%||25%||29%|
|Recurrent cellulitis, gangrene||9%||9%||8%||9%|
Serum Okay and medical outcomes
Among the many 55,183 sufferers from DOPPS phases 1–5 included in end result analyses, median (interquartile vary) follow-up was 16.5 (8.1, 25.5) months and 13,114 (24%) died throughout follow-up, leading to a mortality charge of 16.1 per 100 patient-years. reveals that in contrast with the reference group of SK 4.0–5.0 mEq/L, decrease SK however not increased SK was related to mortality in unadjusted evaluation; nevertheless, after complete multivariable adjustment, significantly for dietary indicators (Desk S1), the form of the affiliation modified, now with increased SK however not decrease SK being related to mortality. Among the many 45,511 sufferers eligible for the cause-specific end result evaluation, 3300 (7%) had an arrhythmia composite occasion throughout follow-up. The adjusted affiliation between SK and the composite arrhythmia end result appeared roughly monotonic, with elevated threat for sufferers with increased SK ranges ().
|HR (95% CI), All-cause mortality||HR (95% CI), Arrhythmia composite^|
|N sufferers (%)||Unadjusted||Adjusted*||Unadjusted||Adjusted*|
|< 4.0||6153 (11%)||1.18 (1.12–1.24)||1.03 (0.97–1.09)||0.99 (0.88–1.11)||0.94 (0.83–1.05)|
|4.0 – 5.0||27107 (50%)||1 (Ref.)||1 (Ref.)||1 (Ref.)||1 (Ref.)|
|5.1 – 5.5||10635 (20%)||0.95 (0.91–0.99)||1.02 (0.97–1.07)||0.97 (0.89–1.07)||1.00 (0.91–1.10)|
|5.6 – 6.0||6238 (11%)||1.02 (0.96–1.08)||1.13 (1.06–1.20)||1.05 (0.95–1.17)||1.07 (0.96–1.20)|
|> 6.0||4403 (8%)||1.00 (0.93–1.07)||1.12 (1.04–1.21)||1.16 (1.02–1.32)||1.21 (1.05–1.38)|
Dialysate Okay and medical outcomes
We noticed increased unadjusted mortality for sufferers with excessive DK (). After complete adjustment for potential confounders, the hazard ratio (HR) (95% CI) for mortality was 0.95 (0.90, 1.00) for sufferers handled with DK 3.0–4.0, and 1.04 (0.97–1.11) for sufferers handled with DK 1.0–1.5 mEq/L, in comparison with the reference group of two.0–2.5 mEq/L. Evaluation of the arrhythmia composite end result can be proven in . Utilizing instrumental variable strategies, the HR (95% CI) per 1 mEq/L increased DK was 0.99 (0.92, 1.07) for all-cause mortality and 0.96 (0.82, 1.12) for the arrhythmia composite end result.
|HR (95% CI), All-cause
|HR (95% CI), Arrhythmia
|Dialysate Okay (mEq/L)||N sufferers (%)||Unadjusted||Adjusted*||Unadjusted||Adjusted*|
|1.0 – 1.5||8114 (15%)||0.96 (0.90–1.03)||1.04 (0.97–1.11)||1.09 (0.95–1.24)||1.14 (1.00–1.30)|
|2.0 – 2.5||33017 (61%)||1 (Ref.)||1 (Ref.)||1 (Ref.)||1 (Ref.)|
|3.0 – 4.0||13405 (25%)||1.13 (1.07–1.18)||0.95 (0.90–1.00)||1.05 (0.96–1.15)||0.95 (0.86–1.04)|
In , we present the associations with medical outcomes of DK 3.0 mEq/L vs. 2.0 mEq/L at numerous ranges of pre-dialysis SK. Once more, the estimated variations in mortality threat had been minimal with HRs starting from 0.94 to 1.03 throughout the 4 SK subgroups, with no discernible sample. Equally, we discovered no associations between DK and the arrhythmia composite end result in any of the SK strata. Additional, there was no proof for impact modification of DK by SK for all-cause mortality (p for interplay = 0.7) or the arrhythmia composite end result (p for interplay = 0.7).
|All sufferers||Pre-dialysis serum Okay (mEq/L)|
|Dialysate Okay (mEq/L)||< 4.0||4.0 – 5.0||5.1 – 6.0||> 6.0|
| DK 3 vs. DK 2
|0.96 (0.91–1.01)||1.03 (0.91–1.17)||0.96 (0.90–1.03)||0.94 (0.85–1.03)||0.97 (0.78–1.20)|
| DK 3 vs. DK 2
|0.98 (0.88–1.08)||1.13 (0.86–1.47)||0.91 (0.80–1.04)||1.06 (0.89–1.27)||1.15 (0.81–1.62)|
Affiliation between dialysate and serum Okay
In a linear regression mannequin adjusted just for DOPPS part and nation, we noticed an inverse affiliation between DK and pre-dialysis SK (−0.35 mEq/L SK per 1 mEq/L DK; 95% CI: −0.37, −0.34). After multivariate adjustment for confounders, the inverse affiliation remained (−0.25, 95% CI: −0.26, −0.24). In an instrumental variable evaluation, nevertheless, we noticed a weak constructive affiliation between DK and SK (+0.09 mEq/L SK per 1 mEq/L DK, 95% CI: +0.05, +0.14). Sensitivity analyses utilizing (1) facility imply DK because the publicity and (2) proscribing to services that prescribed a uniform DK to ≥90% of sufferers resulted in findings per the instrumental variable evaluation.
Within the DOPPS, a big worldwide potential cohort examine of HD sufferers, the place there have been appreciable variations in pre-dialysis SK ranges and apply patterns of DK prescription, excessive SK was related to elevated all-cause mortality and arrhythmia/sudden loss of life after multivariable adjustment. When evaluating the 2 commonest DK prescriptions (DK=3 vs. DK=2 mEq/L), we didn’t discover proof of differential threat of adversarial occasions, general or at any degree of pre-dialysis SK. We additionally noticed solely a minimal impression of DK on pre-dialysis SK in an instrumental variable evaluation designed to attenuate confounding by indication.
In step with prior research, we noticed an elevated threat of each all-cause mortality and an arrhythmia composite end result in sufferers with excessive ranges of SK. Much like Kovesdy et al.,7 the sturdy unadjusted affiliation between hypokalemia and adversarial occasions was considerably confounded and largely attenuated by adjustment for case-mix and indicators of malnutrition, as very low pre-dialysis SK is extra attribute of sufferers in usually poor well being.
The usage of DK < 2 mEq/L has declined throughout examine phases in North America and Europe; in the newest DOPPS part (2012–2015), the proportion of sufferers with DK < 2 mEq/L was down to five% in North America and 16% in Europe/ANZ (solely 6% in Europe/ANZ exterior of Spain). Thus, analyses of DK 1.0–1.5 mEq/L in comparison with 2 mEq/L could also be restricted in scope and generalizability. Since they're probably the most frequent prescriptions and given the dearth of information on their comparative impression of medical outcomes, we centered analyses on the apply of DK=3 vs. 2 mEq/L.
Prior outcomes linking DK degree to medical outcomes have been blended,7, 11, 12 though current editorials advocate avoiding DK < 2 mEq/L, significantly in sufferers with excessive pre-dialysis SK.6,14–18 The potential hazards of very low (< 2 mEq/L) DK are triggered by a bigger elimination of potassium throughout HD inflicting intradialytic and post-dialysis hypokalemia, and infrequently a fast rebound of potassium ranges post-dialysis, contributing to cardiac instability.30 In our major evaluation evaluating extra frequent DK prescriptions, we discovered an analogous threat of adversarial occasions; any variations had been modest and unlikely to be clinically vital. The comparability of all-cause mortality threat utilizing DK ≥ 3.0 vs. 2.0–2.5 mEq/L was qualitatively much like a earlier DOPPS publication, 20 which discovered an 8% elevated threat of mortality for the decrease DK. Jadoul et al.20 noticed a stronger affiliation utilizing instrumental variable analyses, however a bigger pattern measurement of extra up to date sufferers and small variations in methodology used within the present examine mixed to lead to instrumental variable analyses extra per the usual strategies.
Slightly than contemplating serum and dialysate Okay as unbiased threat components, minimizing the potassium gradient, outlined because the distinction between the affected person’s pre-dialysis SK and DK, is commonly really useful.7,31, 32 Nevertheless, a naïve evaluation of gradient Okay and mortality could be pushed by SK as a result of variability in gradient Okay is pushed largely by SK and excessive SK is related to worse outcomes. Additional, an evaluation of gradient Okay adjusted for SK is equivalent to an evaluation of DK adjusted for SK. To extra exactly take a look at whether or not a big Okay gradient is related to adversarial occasions, we as a substitute investigated whether or not a decrease DK (2.0 mEq/L) could be significantly dangerous together with a excessive SK (> 6.0 mEq/L, leading to a gradient Okay > 4.0 mEq/L), however discovered minimal affiliation amongst this subgroup of doubtless high-risk sufferers ().
After accounting for confounding by indication, we noticed solely a minimal impact of DK on pre-dialysis SK. Whereas decrease DK results in decrease SK all through and instantly following the HD session,10,30,33 we’d not anticipate to watch a powerful affiliation with SK ranges measured pre-dialysis, 2–3 days after publicity to DK. Thus interventions to keep away from persistent hyperkalemia, similar to prescription of Okay-binding drugs and/or schooling to cut back dietary Okay consumption, could also be more practical than decreasing DK.
Strengths of our examine embrace a really massive pattern measurement, seize of consultant sufferers in typical care settings, detailed information assortment of potential confounders, causes of loss of life and hospitalization, and appreciable variation in apply patterns which facilitated analyses.
Our examine additionally has a number of limitations. First, due to its observational design, this examine can’t estimate the causal impression of SK and DK on the chance of adversarial occasions. Whereas adjustment for a complete set of potential confounders in each normal Cox regression and instrumental variable analyses helps to mitigate bias, residual confounding could stay. Second, our evaluation of the arrhythmia composite end result is restricted by missingness and potential misclassification of the causes of loss of life and hospitalization; our massive pattern is usually thought of a energy however on this case smaller research could possibly characterize these causes extra uniformly. Third, we didn’t have information on post-dialysis SK. As a result of the affiliation between potassium and adversarial occasions could also be mediated by post-dialysis SK degree, these measurements might have knowledgeable these analyses. Lastly, solely prescribed DK info was out there; in instances the place the affected person could also be individualized to a DK that differs from the prescribed DK for every HD session primarily based on pre-dialysis SK measurement, our information don’t seize the exact DK administered. This can be particularly problematic in instances the place the DK administered throughout the therapy straight previous an arrhythmic occasion differed from the standing prescription. Equally, DK profiling, the various of DK throughout a single HD session,31,32,34 was not captured within the DOPPS and thus we can’t calculate its prevalence nor speculate on its impact on medical outcomes.
Regardless of the restrictions, these findings have vital implications for DK prescribing practices and future analysis. We didn’t discover proof supporting a clinically significant distinction in mortality or arrhythmias evaluating DK of three vs. 2 mEq/L at any degree of pre-dialysis SK, and thus can’t present a suggestion for any fast modifications in apply. Lengthy-term, our outcomes assist equipoise for future analysis of an simply modifiable apply sample in a randomized setting. As beforehand reported, excessive pre-dialysis SK was related to elevated threat of adversarial occasions. Nevertheless, we noticed minimal affiliation between DK and SK measured earlier than dialysis. Together, these outcomes counsel that approaches apart from altering DK focus (e.g., schooling on dietary Okay sources, prescription of Okay-binding drugs) could advantage additional consideration to cut back dangers related to excessive SK.
The DOPPS program is supported by Amgen, Kyowa Hakko Kirin, AbbVie, Sanofi Renal, Baxter Healthcare, and Vifor Fresenius Medical Care Renal Pharma. Extra assist for particular initiatives and nations is supplied by Keryx Biopharmaceuticals, Merck Sharp & Dohme Corp., Proteon Therapeutics, Relypsa, and F. Hoffmann-LaRoche; in Canada by Amgen, BHC Medical, Janssen, Takeda, and the Kidney Basis of Canada (for logistics assist); in Germany by Hexal, DGfN, Shire, and the WiNe Institute; and for PDOPPS in Japan by the Japanese Society for Peritoneal Dialysis (JSPD). All assist is supplied with out restrictions on publications.
SMB is employed by DaVita has been on advisory boards for Keryx, Otsuka, Bayer, AstraZeneca. SMB’s spouse is employed by AstraZeneca. LAU is employed by and owns inventory in Fresenius Medical Care. DEW receives wage assist for analysis initiatives from Dialysis Clinic Inc. FWM is employed by and owns inventory in Fresenius Medical Care. ARN is employed by DaVita. Dr. Jadoul has been a speaker for Fresenius Pharma (advertising and marketing Sorbisterit = Okay binder) and took part in an Advert Board organized by ZS Pharma (different Okay binder beneath growth). WCW studies having acquired honoraria for service on scientific advisory, occasion adjudication, or information security monitoring boards for Akebia, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Medtronic, Relypsa, Vifor Fresenius Medical Care Renal Pharma, and Zoll. BMR has acquired speaker charges for Kyowa Hakko Kirin. FT has acquired honorarium from DSI and is a member of the AAKP medical advisory board. The opposite authors declare that they don’t have any related monetary pursuits.