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Symptom burden and patient experience

TL;DR — Fatigue, pruritus, sleep disturbance, pain, restless legs, cognitive difficulty and treatment burden are common across advanced CKD, yet routine evidence systems prioritize laboratory and survival endpoints. IPOS-Renal provides a validated symptom instrument (Raj 2018, PMID 29729346); SONG-HD identified fatigue and life participation as core outcomes through patient-professional consensus (Ju 2018, PMID 29551585) (Tong 2017, PMID 27497527). Difelikefalin produced at least a 3-point itch improvement in 49.1% versus 27.9% at 12 weeks in KALM-1, with more diarrhoea, dizziness and vomiting (Fishbane 2020, PMID 31702883). Symptom monitoring is feasible, but evidence that feedback alone changes outcomes remains developing (Agarwal 2023, PMID 37993776).

Symptom clusters

Symptoms co-occur and vary by stage, dialysis exposure, anaemia, mood, sleep and comorbidity. Attribution to uraemia alone can miss treatable causes.

Fatigue

In a Dutch nationwide survey of 414 patients (144 CKD without kidney replacement therapy, 39 on dialysis, 231 after transplantation), 94.7% experienced fatigue often, 90.3% for more than six months, and 86.3% ranked it among their three most burdensome symptoms; younger patients were limited in more life domains than older ones. Yet 32.1% never or rarely discussed fatigue with a physician, 67.8% received no treatment for it, and 58.6% felt the advice or treatment given did not manage it (Schade van Westrum 2025, PMID 40599823).

Pruritus

KALM-1 showed a 21.2-point absolute increase in a 3-point WI-NRS response after imputation (Fishbane 2020, PMID 31702883). Benefit was measured in haemodialysis, not all CKD.

Life participation

Patients consistently prioritize ability to work, study, care and participate. Consensus workshops with 130 participants (74 patients and caregivers, 56 health professionals) from 18 countries supported SONG-Life Participation as the core outcome measure for CKD not requiring kidney replacement therapy, while stating explicitly that the measure still needs piloting and validation in that population (Hughes 2025, PMID 40569671).

Treatment burden

Diet, polypharmacy, appointments, transport and dialysis time create workload. Burden is an outcome and an effect modifier for adherence.

Patient-voice method

The literature layer synthesizes public sources in aggregate, paraphrases rather than extracting private testimony, and records coverage limitations.

Patient-priority outcome map

Domain Measure/evidence Quantitative or methodological anchor
Multi-symptom burden IPOS-Renal Validated in advanced kidney disease (Raj 2018, PMID 29729346)
Fatigue SONG-HD fatigue work Core outcome and standard-measure development (Ju 2018, PMID 29551585)
Life participation SONG workshops (130 participants, 18 countries) Core measure endorsed by consensus; piloting and validation in non-KRT CKD still outstanding (Hughes 2025, PMID 40569671)
Pruritus Worst Itching Intensity NRS ≥3-point response 49.1% vs 27.9% with difelikefalin (Fishbane 2020, PMID 31702883)
Routine symptom feedback SWIFT pilot Feasible cluster-registry design; effectiveness unresolved (Agarwal 2023, PMID 37993776)
Treatment-free time Dialysis/CKM decision literature Rarely co-reported with survival (Buur 2021, PMID 34507554)
Work and role function Nationwide patient survey (n=414) Fatigue often experienced by 94.7%; 32.1% never/rarely discuss it with a physician (Schade van Westrum 2025, PMID 40599823)

The symptom burden, quantified globally

The largest synthesis to date searched MEDLINE, PsycINFO and CINAHL for cross-sectional and longitudinal studies published between January 2000 and September 2021 reporting patient-reported symptom prevalence, severity or health-related quality of life in adults with CKD, and pooled 449 studies with 199,147 participants from 62 countries, stratified into non-RRT CKD, dialysis and transplant groups. Studies used 67 different outcome measures covering 68 distinct reported symptoms. Fatigue was the most prevalent: 70% (95% CI 60–79) in 14 studies of 4,139 participants not on kidney replacement therapy, and comparably high on dialysis (Fletcher 2022, PMID 35385471).

Two structural facts follow. A 70% prevalence in pre-dialysis CKD contradicts the common framing of symptom burden as a dialysis problem. And 67 instruments across 449 studies is the measurement problem in one number — the literature cannot be pooled precisely because almost every study chose its own instrument.

Chronic pain is the second dominant symptom and equally under-treated. Pooling 68 studies of adults with GFR category 3–5 CKD including dialysis and conservatively managed patients, the review estimated prevalence of overall chronic pain along with musculoskeletal, bone/joint, muscle and neuropathic subtypes, and calibrated severity scores to a common 0–10 scale (Davison 2021, PMID 33680484).

Fatigue: from a complaint to a measurable endpoint

Fatigue is consistently ranked by patients and clinicians among the highest-priority outcomes, yet has been infrequently and inconsistently reported in haemodialysis trials. The SONG-HD consensus workshop convened 15 patients and caregivers with 42 health professionals from nine countries and identified four requirements for a core measure: recognising fatigue as a distinct multifaceted symptom, emphasising its impact on life participation, ensuring relevance and accuracy to support shared decision-making, and minimising administration burden (Ju 2018, PMID 29551585). The resulting SONG-HD Fatigue instrument was validated longitudinally at three time points in 485 participants across haemodialysis units in the United Kingdom, Australia and Romania, assessing internal consistency, test–retest reliability, convergent validity against the fatigue visual analogue scale, SF-12 and FACIT-Fatigue, and confirmatory factor structure (Ju 2020, PMID 33093215).

The qualitative evidence explains why a severity score alone is insufficient. Thematic synthesis of 65 qualitative studies involving 1,713 haemodialysis patients identified fatigue as a debilitating burden of dialysis (bodily depletion, post-dialysis exhaustion, vigilance and worry inhibiting rest, a regimen without relief), restricted life participation (deprived of time, managing energy reserves, joys foregone) and diminished capacity to fulfil relationship roles including work, parenting and sexual intimacy (Jacobson 2019, PMID 30955947). Life participation, not fatigue intensity, is what patients describe as the loss.

Uraemic pruritus: an interventional endpoint that moved

Difelikefalin, a peripherally restricted selective kappa-opioid receptor agonist, was tested in 378 haemodialysis patients with moderate-to-severe pruritus randomized to intravenous difelikefalin 0.5 µg/kg or placebo three times weekly for 12 weeks. A decrease of at least 3 points on the 24-hour Worst Itching Intensity Numerical Rating Scale occurred in 82/158 (51.9%) versus 51/165 (30.9%), with imputed percentages 49.1% versus 27.9% (p < 0.001). Itch-related quality of life improved on both the 5-D itch and Skindex-10 scales, and the more demanding ≥4-point response was reached by an imputed 37.1% versus 17.9% (Fishbane 2020, PMID 31702883).

The placebo response of 27.9–30.9% is itself the finding to carry forward: nearly a third of the control arm met the response threshold, which sets the bar for any uncontrolled report of symptom improvement in this population.

Exercise: functional effects in randomized trials

During dialysis. A multicentre cluster randomized trial assigned 1,211 patients (917 analysed; mean age 65.9 ± 14.4, 38.9% female) to combined endurance and resistance training during haemodialysis or usual care. At 12 months, 60-second sit-to-stand repetitions rose from 16.2 ± 7.6 to 19.2 ± 9.1 with exercise and fell from 16.2 ± 7.1 to 14.7 ± 7.9 with usual care (group difference 3.85 repetitions; 95% CI 2.22–5.48; p < 0.0001). Timed up-and-go improved by 1.1 seconds (95% CI 0.3–1.9) and 6-minute walk distance by 37.5 m (14.7–60.4). The SF-36 physical summary and vitality subscales differed; other subscales did not. Median annual hospital days were 2 with exercise versus 5 with usual care, adverse events during sessions were similar, and mortality was unaffected (Anding-Rost 2023, PMID 38320198).

Before dialysis. In 99 adults aged ≥55 with eGFR 15–<45 (mean age 68, 62% African American, mean eGFR 33, 59% with diabetes) randomized to 12 months of supervised in-centre exercise or group health education, only 59% of exercise sessions were attended in the first six months. Peak oxygen consumption was higher in the exercise arm at 6 months (17.9 ± 5.5 versus 15.9 ± 7.0 mL/kg/min; p = 0.03) but the difference was not sustained at 12 months; 6-minute walk distance improved by an adjusted 98 feet (p = 0.02; treatment-by-time interaction p = 0.03) and timed up-and-go improved (p = 0.04), without excess adverse events (Weiner 2023, PMID 35944747).

The contrast between the sustained gains in the larger intradialytic trial and the faded fitness difference in the smaller pre-dialysis trial may partly reflect adherence and delivery: intradialytic exercise occurs during an appointment the patient is already attending.

Symptom or intervention Quantity Source
Fatigue prevalence, non-RRT CKD 70% (60–79), 14 studies, 4,139 participants Fletcher 2022, PMID 35385471
Instruments in use 67 measures across 449 studies, 68 symptoms Fletcher 2022, PMID 35385471
Chronic pain Pooled across 68 studies, G3–G5 including dialysis and conservative care Davison 2021, PMID 33680484
Core fatigue measure SONG-HD Fatigue validated in 485 patients, 3 countries Ju 2020, PMID 33093215
Difelikefalin for pruritus ≥3-point WI-NRS response 51.9% vs 30.9% (imputed 49.1% vs 27.9%) Fishbane 2020, PMID 31702883
Intradialytic exercise STS60 difference 3.85 reps (2.22–5.48); hospital days 2 vs 5/year Anding-Rost 2023, PMID 38320198
Pre-dialysis exercise VO2peak difference at 6 months not sustained at 12; 6MWT +98 feet Weiner 2023, PMID 35944747

Depression: acceptance is not the barrier, and the two treatments are not equivalent

A two-phase multicentre randomized trial across 41 dialysis facilities in three US metropolitan areas enrolled patients on haemodialysis for at least three months with a Beck Depression Inventory-II score of 15 or greater. Phase 1 randomized 184 patients to an engagement interview or a control visit; the proportion initiating depression treatment within 28 days was 66% versus 64% (p = 0.77; risk difference 2.1, 95% CI −12.1 to 16.4) — the engagement intervention did nothing, and two-thirds of patients accepted treatment either way. Phase 2 randomized 120 of them to 12 weeks of cognitive behavioural therapy delivered in the dialysis facility or to sertraline; sertraline produced lower Quick Inventory of Depressive Symptoms-Clinician-Rated scores at 12 weeks (effect estimate −1.84, 95% CI −3.54 to −0.13; p = 0.035), with more frequent adverse events (Mehrotra 2019, PMID 30802897).

Two results deserve to be separated. The phase 1 finding refutes the common assumption that patients on dialysis decline mental health treatment — acceptance was about two-thirds without any intervention. The phase 2 finding is a modest advantage for sertraline on a clinician-rated scale over 12 weeks, purchased with more adverse events, with no untreated comparator and no assessment of durability. The authors state both limitations explicitly.

Sleep: three distinct disorders, one under-recognised cluster

Sleep disorders are highly prevalent in CKD and routinely under-recognised, and they are not one entity.

Restless legs syndrome is common in CKD through disturbed dopamine metabolism and is exacerbated by iron deficiency and uraemia, producing poor sleep quality and daytime fatigue — which connects it directly to the anaemia and iron management discussed on anaemia of CKD and to the fatigue burden described above.

Insomnia is prevalent, particularly in dialysis-treated patients, with increased sleep latency and sleep fragmentation; suggested contributors include poor sleep habits, frequent napping during dialysis sessions, uraemia, medications and mood disorders.

Sleep apnoea has a bidirectional relationship with CKD: it is a risk factor for accelerated CKD progression, while the fluid overload associated with kidney failure can cause both obstructive and central sleep apnoea. Its presence compounds already elevated cardiovascular morbidity and mortality in this population as well as causing daytime fatigue and reduced quality of life (Lyons 2024, PMID 38789686).

The clinical consequence is that "fatigue", the symptom with roughly 70% prevalence in CKD (Fletcher 2022, PMID 35385471), is not a single target. At least three treatable sleep disorders sit underneath it, two of which have specific and available interventions (iron repletion for restless legs, positive airway pressure for apnoea) and one of which — napping during dialysis — is generated by the treatment itself.

Decision and interpretation matrix

Dimension Question Guardrail
Diagnostic axis Cause + G category + A category Avoid treating eGFR as the diagnosis
Time axis Chronicity and trajectory Separate acute change from persistent disease
Risk axis Kidney failure + cardiovascular events + death Show competing events
Treatment axis Eligibility, absolute benefit, harm, burden Do not rank drugs by relative effect alone
Measurement axis Assay, equation, repeatability State what was actually measured
Equity axis Testing, referral, access, affordability Audit downstream care, not labels only
Patient axis Symptoms, function, life participation Include outcomes patients prioritize
Evidence axis RCT, cohort, model, guideline Do not collapse designs

Evidence ledger

This ledger makes the page’s evidentiary mix inspectable. It does not imply that every source answers every question.

PMID Record used Role and boundary
29729346 Validation of the IPOS-Renal Symptom Survey in Advanced Kidney Disease. (Raj 2018, PMID 29729346) Observational or conceptual evidence; association is not treatment effect.
29551585 Establishing a Core Outcome Measure for Fatigue in Patients on Hemodialysis. (Ju 2018, PMID 29551585) Consensus or priority-setting exercise; it records participant judgement, not measured outcomes.
27497527 Establishing Core Outcome Domains in Hemodialysis: SONG-HD consensus workshop. (Tong 2017, PMID 27497527) Consensus or priority-setting exercise; it records participant judgement, not measured outcomes.
31702883 A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus. (Fishbane 2020, PMID 31702883) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
37993776 Feasibility of Symptom monitoring WIth Feedback Trial for adults on hemodialysis. (Agarwal 2023, PMID 37993776) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
40599823 Fatigue across different chronic kidney disease populations: experiences and needs of patients. (Schade van Westrum 2025, PMID 40599823) Observational or conceptual evidence; association is not treatment effect.
40569671 Core Outcome Measure for Life Participation in Patients with CKD. (Hughes 2025, PMID 40569671) Consensus or priority-setting exercise; it records participant judgement, not measured outcomes.
34507554 Does conservative kidney management offer a quantity or quality of life benefit compared to dialysis? A systematic review. (Buur 2021, PMID 34507554) Synthesis; heterogeneity and included-study definitions constrain transport.
38490803 KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. (KDIGO CKD Work Group 2024, PMID 38490803) Guideline or commentary; recommendation evidence depends on its review.
38519239 Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. (Levin 2024, PMID 38519239) Guideline or commentary; recommendation evidence depends on its review.
32061315 Global, regional, and national burden of chronic kidney disease, 1990-2017. (GBD CKD Collaboration 2020, PMID 32061315) Modelled projection; the estimate follows from the model inputs and assumptions, not from observed randomized follow-up.
22038337 A population-based approach for the definition of chronic kidney disease: CKD Prognosis Consortium. (Cirillo 2012, PMID 22038337) Synthesis; heterogeneity and included-study definitions constrain transport.
23243116 Cohort profile: the chronic kidney disease prognosis consortium. (Matsushita 2013, PMID 23243116) Observational or conceptual evidence; association is not treatment effect.
37787795 Estimated GFR, Albuminuria, and Adverse Outcomes: individual-participant data meta-analysis. (CKD Prognosis Consortium 2023, PMID 37787795) Synthesis; heterogeneity and included-study definitions constrain transport.
30348535 Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities. (Inker 2019, PMID 30348535) Synthesis; heterogeneity and included-study definitions constrain transport.
34554658 New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. (Inker 2021, PMID 34554658) Observational or conceptual evidence; association is not treatment effect.
34563581 A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. (Delgado 2022, PMID 34563581) Guideline or commentary; recommendation evidence depends on its review.
26757465 Multinational assessment of equations predicting kidney failure. (Tangri 2016, PMID 26757465) Synthesis; heterogeneity and included-study definitions constrain transport.
20581422 A randomized, controlled trial of early versus late initiation of dialysis. (Cooper 2010, PMID 20581422) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
28538218 Dialysis Therapy and Conservative Management of Advanced Chronic Kidney Disease in the Elderly: A Systematic Review. (Wongrakpanich 2017, PMID 28538218) Synthesis; heterogeneity and included-study definitions constrain transport.
35285915 Long-term Outcomes Among Patients With Advanced Kidney Disease Who Forgo Maintenance Dialysis: A Systematic Review. (Wong 2022, PMID 35285915) Synthesis; heterogeneity and included-study definitions constrain transport.
41363177 Conservative kidney management versus dialysis for stage 5 chronic kidney disease in older people. (Yang 2025, PMID 41363177) Synthesis; heterogeneity and included-study definitions constrain transport.
37429259 Kidney Supportive Care for Working-Age Adults with Chronic Kidney Disease: symptom burden. (Liu 2024, PMID 37429259) Observational or conceptual evidence; association is not treatment effect.
31295050 A Descriptive Analysis of an Ambulatory Kidney Palliative Care Program. (Scherer 2020, PMID 31295050) Observational or conceptual evidence; association is not treatment effect.
32673242 Characteristics, Symptom Severity, and Experiences of Patients Reporting CKD in an Online Health Community. (James 2020, PMID 32673242) Observational or conceptual evidence; association is not treatment effect.
28238554 Developing a Set of Core Outcomes for Trials in Hemodialysis: International Delphi Survey. (Evangelidis 2017, PMID 28238554) Consensus or priority-setting exercise; it records participant judgement, not measured outcomes.

What can and cannot be concluded

  • Risk associations do not by themselves establish that changing the marker changes risk.
  • A relative effect must be paired with baseline risk, follow-up and the exact endpoint.
  • Albuminuria, acute eGFR change, chronic eGFR slope and kidney failure are not interchangeable.
  • Subgroup consistency is not evidence that every subgroup had adequate power.
  • Guideline recommendations combine evidence with values, feasibility, cost and service capacity.
  • Older adults require competing-mortality and treatment-burden framing.
  • Dialysis and transplantation comparisons are vulnerable to eligibility and immortal-time bias.
  • Modelled lifetime benefit is not a randomized observed benefit.
  • A biochemical response without a patient-important outcome remains a surrogate result.
  • This page is research synthesis, not individualized medical advice.

Research-design checklist

  • Define CKD cause, G category, A category and chronicity at baseline.
  • Report the creatinine or cystatin C equation and laboratory calibration.
  • Prespecify acute and chronic eGFR slopes when haemodynamic effects are expected.
  • Keep sustained GFR decline, kidney failure and replacement therapy separable.
  • Report absolute event risks, follow-up and confidence intervals with relative effects.
  • Treat death as a competing event where it can preclude kidney failure.
  • Measure hyperkalaemia, acute kidney injury and treatment discontinuation consistently.
  • Include symptoms, function, life participation and treatment burden.
  • Describe background RAS, SGLT2, MRA and GLP-1 therapy explicitly.
  • Prespecify albuminuria and cause strata without over-reading underpowered interactions.
  • Record screening, prescribing, persistence and monitoring as separate implementation steps.
  • Report representation, access and affordability variables needed for equity analysis.

Open questions

  • Does routine symptom monitoring with feedback improve life participation, or only measurement? SWIFT established feasibility with a 54% intervention-arm response rate; a definitive trial was still under way (Agarwal 2023, PMID 37993776). → OQ-8
  • What is the minimum clinically important difference for CKD fatigue, and does it differ between non-dialysis CKD, dialysis and transplantation (Ju 2018, PMID 29551585) (Schade van Westrum 2025, PMID 40599823)? → OQ-18
  • Does difelikefalin's haemodialysis pruritus benefit transfer to non-dialysis CKD? KALM-1 enrolled only haemodialysis patients (Fishbane 2020, PMID 31702883).

  • Why do 32.1% of patients never or rarely discuss fatigue with a physician, and what changes that (Schade van Westrum 2025, PMID 40599823)?

  • Can the CKD symptom literature be pooled at all when 449 studies used 67 different instruments to describe 68 symptoms (Fletcher 2022, PMID 35385471)? Adoption of the validated SONG-HD fatigue measure (Ju 2020, PMID 33093215) would test this within one symptom.

  • Why is fatigue prevalence ~70% before kidney replacement therapy, and what is modifiable about it (Fletcher 2022, PMID 35385471)?
  • Does the sustained functional benefit of intradialytic exercise (STS60 +3.85 repetitions, hospital days 2 vs 5) translate to any outcome beyond physical performance, given unchanged mortality (Anding-Rost 2023, PMID 38320198)?

  • What explains a 27.9–30.9% placebo response rate for uraemic pruritus, and how should uncontrolled symptom reports be interpreted against it (Fishbane 2020, PMID 31702883)?

  • Does treating depression in dialysis patients change anything beyond symptom scores? The only head-to-head trial had no untreated arm and did not assess persistence of effect (Mehrotra 2019, PMID 30802897).

  • If two-thirds of patients accept depression treatment without any engagement intervention (66% vs 64%), why is depression under-treated in dialysis populations (Mehrotra 2019, PMID 30802897)?

  • How much of the ~70% fatigue prevalence in CKD is attributable to treatable sleep disorders — restless legs, insomnia, sleep apnoea — rather than to uraemia or anaemia (Lyons 2024, PMID 38789686) (Fletcher 2022, PMID 35385471)?

  • Does treating sleep apnoea slow CKD progression, given the reported bidirectional relationship (Lyons 2024, PMID 38789686)?

References

  1. Raj et al. Validation of the IPOS-Renal Symptom Survey in Advanced Kidney Disease. J Pain Symptom Manage. 2018;56(2):281-287. PMID 29729346
  2. Ju et al. Establishing a Core Outcome Measure for Fatigue in Patients on Hemodialysis. Am J Kidney Dis. 2018;72(1):104-112. PMID 29551585
  3. Tong et al. Establishing Core Outcome Domains in Hemodialysis: SONG-HD consensus workshop. Am J Kidney Dis. 2017;69(1):97-107. PMID 27497527
  4. Fishbane et al. A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus. N Engl J Med. 2020;382(3):222-232. PMID 31702883
  5. Agarwal et al. Feasibility of Symptom monitoring WIth Feedback Trial for adults on hemodialysis. BMC Nephrol. 2023;24(1):345. PMID 37993776
  6. Schade van Westrum et al. Fatigue across different chronic kidney disease populations: experiences and needs of patients. Clin Kidney J. 2025;18(5):sfaf118. PMID 40599823
  7. Hughes et al. Core Outcome Measure for Life Participation in Patients with CKD. Clin J Am Soc Nephrol. 2025;20(8):1041-1050. PMID 40569671
  8. Buur et al. Does conservative kidney management offer a quantity or quality of life benefit compared to dialysis? A systematic review. BMC Nephrol. 2021;22(1):307. PMID 34507554
  9. KDIGO CKD Work Group et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-S314. PMID 38490803
  10. Levin et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int. 2024;105(4):684-701. PMID 38519239
  11. GBD CKD Collaboration et al. Global, regional, and national burden of chronic kidney disease, 1990-2017. Lancet. 2020;395(10225):709-733. PMID 32061315
  12. Cirillo et al. A population-based approach for the definition of chronic kidney disease: CKD Prognosis Consortium. J Nephrol. 2012;25(1):7-12. PMID 22038337
  13. Matsushita et al. Cohort profile: the chronic kidney disease prognosis consortium. Int J Epidemiol. 2013;42(6):1660-1668. PMID 23243116
  14. CKD Prognosis Consortium et al. Estimated GFR, Albuminuria, and Adverse Outcomes: individual-participant data meta-analysis. JAMA. 2023;330(13):1266-1277. PMID 37787795
  15. Inker et al. Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities. Am J Kidney Dis. 2019;73(2):206-217. PMID 30348535
  16. Inker et al. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021;385(19):1737-1749. PMID 34554658
  17. Delgado et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. Am J Kidney Dis. 2022;79(2):268-288.e1. PMID 34563581
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  19. Cooper et al. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med. 2010;363(7):609-619. PMID 20581422
  20. Wongrakpanich et al. Dialysis Therapy and Conservative Management of Advanced Chronic Kidney Disease in the Elderly: A Systematic Review. Nephron. 2017;137(3):178-189. PMID 28538218
  21. Wong et al. Long-term Outcomes Among Patients With Advanced Kidney Disease Who Forgo Maintenance Dialysis: A Systematic Review. JAMA Netw Open. 2022;5(3):e222255. PMID 35285915
  22. Yang et al. Conservative kidney management versus dialysis for stage 5 chronic kidney disease in older people. Cochrane Database Syst Rev. 2025;12(12):CD015151. PMID 41363177
  23. Liu et al. Kidney Supportive Care for Working-Age Adults with Chronic Kidney Disease: symptom burden. Nephron. 2024;148(1):34-42. PMID 37429259
  24. Scherer et al. A Descriptive Analysis of an Ambulatory Kidney Palliative Care Program. J Palliat Med. 2020;23(2):259-263. PMID 31295050
  25. James et al. Characteristics, Symptom Severity, and Experiences of Patients Reporting CKD in an Online Health Community. J Med Internet Res. 2020;22(7):e18548. PMID 32673242
  26. Evangelidis et al. Developing a Set of Core Outcomes for Trials in Hemodialysis: International Delphi Survey. Am J Kidney Dis. 2017;70(4):464-475. PMID 28238554
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  30. Jacobson J, et al. Patient Perspectives on the Meaning and Impact of Fatigue in Hemodialysis: A Systematic Review and Thematic Analysis of Qualitative Studies. Am J Kidney Dis. 2019;74(2):179-192. PMID 30955947
  31. Anding-Rost K, et al. Exercise during Hemodialysis in Patients with Chronic Kidney Failure. NEJM Evid. 2023;2(9):EVIDoa2300057. PMID 38320198
  32. Weiner DE, et al. Effect of Long-term Exercise Training on Physical Performance and Cardiorespiratory Function in Adults With CKD: A Randomized Controlled Trial. Am J Kidney Dis. 2023;81(1):59-66. PMID 35944747
  33. Mehrotra R, et al. Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized Clinical Trial. Ann Intern Med. 2019;170(6):369-379. PMID 30802897
  34. Lyons OD, et al. Sleep disorders in chronic kidney disease. Nat Rev Nephrol. 2024;20(10):690-700. PMID 38789686