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Low cystatin C estimate signals higher risk
When the cystatin C–based kidney filtration estimate is ≥30% lower than the creatinine-based estimate, long-term death, heart, and kidney risks are higher.
*Individual-participant meta-analysis of cohort studies; Level 1a (OCEBM).

Citation

Estrella MM, Ballew SH, Sang Y, et al; Chronic Kidney Disease Prognosis Consortium. Discordance in creatinine- and cystatin C–based estimated kidney filtration rate and clinical outcomes: a meta-analysis. JAMA. 2025;334(21):1915-1926. doi:10.1001/jama.2025.17578

Background

Kidney function is often estimated from blood creatinine, but this marker can be influenced by factors unrelated to kidney filtering. Cystatin C is an alternative blood marker; differences between the 2 estimates may identify patients at higher risk.

Patients

821,327 adults from 23 outpatient cohorts; 39,639 adults from 2 hospital cohorts.

Intervention

Cystatin C–based kidney filtration estimate ≥30% lower than creatinine-based estimate.

Control

Difference between −30% and +30% (reference group).

Outcome

Death (all-cause; cardiovascular), major artery disease events, heart failure, and kidney failure needing dialysis or transplant.

Follow-up Period

Outpatients: mean 11 years (hospital cohorts not used for long-term outcomes).

Results

Finding Key results
How common was a ≥30% lower cystatin C estimate? Outpatients: 11%; Hospitalized patients: 35%.
All-cause death (primary) Higher risk: Hazard ratio 1.69 (95% confidence interval, 1.57-1.82); excess 11.6 deaths/1000 person-years (Number needed to harm ≈86 person-years). Lower risk when cystatin C estimate was ≥30% higher: 0.76 (0.73-0.80); Number needed to treat ≈256 person-years.
Cardiovascular death Higher: 1.61 (1.48-1.76); Number needed to harm ≈435 person-years. Lower: 0.79 (0.67-0.91); Number needed to treat ≈1250 person-years.
Major artery disease events Higher: 1.35 (1.27-1.44); Number needed to harm ≈286 person-years. Lower: 0.81 (0.74-0.89); Number needed to treat ≈556 person-years.
Heart failure Higher: 1.54 (1.40-1.68); Number needed to harm ≈217 person-years. Lower: 0.76 (0.69-0.84); Number needed to treat ≈476 person-years.
Kidney failure needing dialysis or transplant Higher: 1.29 (1.13-1.47); Number needed to harm ≈1667 person-years. Lower: NS.

Limitations

Observational cohorts; lab methods varied; many outcomes based on diagnosis codes; selection bias for cystatin C testing; limited data on muscle mass and other confounders; hospital outcomes not tracked long term.

Funding

National Kidney Foundation and US federal kidney institute; no funder role reported.

Clinical Application

Consider ordering cystatin C (or a combined estimate) when creatinine may mislead—older, hospitalized, heart failure, liver disease, obesity, or smokers—to improve risk assessment and care planning.

Top Journal Rankings - February 2026

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14 abstracts scored across 7 criteria. Click any article to expand criterion scores.
1. 7.0
Effect of Continuity of Care on Emergency Care and Hospital Admissions Among Patients Receiving Home-Based Care: A Population-Based Cohort Study.
Overall: A primary-care cohort study in very old home-care patients links higher GP/nurse continuity with fewer urgent-care visits and hospitalizations, but observational design and limited precision reporting constrain confidence in causality and the size of benefit.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Conducted in primary health care centers and focused on continuity with GPs and nurses for home-based care patients—an issue directly relevant to primary care organization and outcomes in frail older adults.
Validity, Bias Control & Precision 5.5
Population-based cohort with adjusted mixed logistic models and Cox models, but observational design leaves substantial residual confounding/selection bias risk; the abstract does not report confidence intervals or detailed model performance, limiting precision appraisal.
Patient-Oriented Outcomes 8.5
Urgent care use and hospital admissions are clearly patient-important, utilization-related outcomes rather than surrogate physiologic markers.
Magnitude of Net Benefit 6.5
Associations appear potentially large (odds ratios reported as ≤0.45), but absolute risk differences, event rates, and potential downsides or tradeoffs of pursuing higher continuity are not provided, making net benefit hard to quantify.
Implementability & Practicality 6.0
Improving continuity to a ≥75% visit threshold is conceptually straightforward, but achieving it may require scheduling, staffing, and system-level changes; the abstract does not describe specific interventions to operationalize this.
Practice-Changing Potential 6.5
Suggests a practical continuity target that could influence care models for homebound older adults, but as a single observational study without clear causal inference or absolute effects, it is more hypothesis-supporting than definitively practice-changing.
2. 5.7
General practice consultation patterns and patient factors predicting older patients' use of out-of-hours services: a nationwide register-based cohort study.
Overall: A highly relevant nationwide observational study suggesting patient factors drive out-of-hours use more than daytime consultation volume, but it focuses on utilization rather than health outcomes and cannot establish causal, practice-changing effects.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Directly addresses general practice daytime access and older patients’ use of out-of-hours primary care, a common primary-care organizational and clinical-triage issue.
Validity, Bias Control & Precision 7.0
Nationwide register-based cohort with multivariable modeling and appropriate count-data methods, but it remains observational with potential residual confounding and the abstract provides no effect sizes or confidence intervals.
Patient-Oriented Outcomes 4.0
The main outcome is healthcare utilization (out-of-hours contacts) rather than health outcomes such as morbidity, hospitalization, function, or quality of life.
Magnitude of Net Benefit 3.0
This is not an intervention study and reports largely that more daytime consultations were not associated with fewer out-of-hours visits, without quantifying benefits, harms, or patient burden.
Implementability & Practicality 6.0
Findings are easy to understand and could inform practice planning, but changing consultation volume or organization is operationally complex and the study does not test an implementable strategy.
Practice-Changing Potential 5.0
Suggests that expanding daytime consultation volume alone may not reduce out-of-hours use, which may influence assumptions, but evidence is context-specific (Denmark) and nonrandomized.
3. 5.5
Health problems of people with intellectual disabilities in general practice: dynamic cohort study between 2012 and 2021 with Dutch routine care data.
Overall: A highly primary-care–relevant, large routine-data cohort describing higher contact rates and broader morbidity in adults with intellectual disabilities, but limited by retrospective design details, lack of precision metrics, and no tested intervention or patient-centered outcome impact.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Uses routine general-practice data across >80 Dutch practices and focuses on common GP encounters, diagnoses, and prescribing in adults with intellectual disabilities versus matched controls.
Validity, Bias Control & Precision 6.0
Large, multi-practice retrospective matched cohort supports descriptive comparisons, but the abstract provides no effect estimates with confidence intervals and residual confounding/misclassification are likely in routine-data ID identification.
Patient-Oriented Outcomes 4.5
Reports contacts, symptoms/diagnoses, and prescribing patterns (healthcare use and clinical labels) rather than patient-centered outcomes like quality of life, functional status, hospitalizations, or mortality.
Magnitude of Net Benefit 2.0
This is an observational characterization study and does not evaluate an intervention or quantify benefits versus harms/burdens; reported differences (e.g., more contacts, higher depression prevalence) do not translate to net benefit.
Implementability & Practicality 6.0
Findings are easy to understand and could inform vigilance and care planning in primary care, but the abstract does not specify actionable interventions or workflows to implement.
Practice-Changing Potential 5.5
May reinforce the need for tailored GP care for patients with intellectual disabilities, but conclusions largely mirror prior findings and do not provide a concrete, new management change.
4. 5.5
Budget Impact Analysis of the Balanced Opioid Initiative: A Cluster Randomized Trial Aimed at Deprescribing Opioids for Chronic Pain in Primary Care Settings.
Overall: A pragmatic primary-care cluster trial with useful cost/budget findings for opioid deimplementation, but it mainly reports prescribing/process outcomes and lacks effect-size/precision details, making patient impact and net benefit hard to judge.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Targets guideline-concordant opioid prescribing and deprescribing for chronic pain in 32 primary care clinics, a common and actionable primary-care problem.
Validity, Bias Control & Precision 6.0
Cluster randomized design across multiple clinics supports causal inference, but the abstract provides no effect sizes, confidence intervals, or key analytic details for either prescribing or utilization outcomes, limiting precision and bias appraisal.
Patient-Oriented Outcomes 2.0
Primary and secondary outcomes are prescribing dose (MME) and process measures (screening/agreements/urine testing) rather than patient-centered outcomes such as pain, function change, overdose, or quality of life.
Magnitude of Net Benefit 4.0
Reports decreased mean MME and increased pain/function screening, but also decreased treatment agreements and urine drug screening; without patient outcomes or quantified effect sizes, the overall benefit-versus-harm balance is uncertain.
Implementability & Practicality 7.0
Educational meetings, audit/feedback, practice facilitation, and peer consulting are feasible health-system interventions, though they require staff time/coordination and have nontrivial per-clinic costs.
Practice-Changing Potential 5.0
Provides comparative budget impact information that could influence how clinics choose implementation strategies, but the lack of patient outcome evidence and missing effect magnitudes limits immediate practice change.
5. 5.3
Patients' experiences of a patient-centred polypharmacy medication review intervention: a mixed-methods study.
Overall: Highly relevant to primary care and plausibly implementable, but the abstract reports limited results focused on satisfaction without effect sizes, clinical outcomes, or harms, so impact and credibility are difficult to assess.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Focuses on polypharmacy medication review delivered in primary care, a common generalist responsibility and decision point.
Validity, Bias Control & Precision 3.0
Mixed-methods process evaluation within an RCT, but the abstract provides minimal quantitative results (survey response rate only) and no precision metrics, limiting confidence in findings.
Patient-Oriented Outcomes 6.0
Assesses patient experience and satisfaction (patient-important), but does not report clinical outcomes, harms, or objective health endpoints.
Magnitude of Net Benefit 3.0
Claims potential improvements in experience/engagement but provides no effect sizes or harms/burdens, so net benefit cannot be judged from the abstract.
Implementability & Practicality 7.0
A patient-centred medication review is broadly feasible in routine primary care, though the abstract suggests preparation/support needs that could add workflow burden.
Practice-Changing Potential 4.0
Supports the importance of communication and person-centred approaches, but without demonstrated outcome improvements it is more confirmatory than practice-changing.
6. 5.2
Clinical assessment of recurrent cancer: a Danish cohort study in general practice.
Overall: Highly relevant to primary care, but observational design with substantial nonresponse and reliance on diagnostic interval outcomes limits confidence and practice-changing impact.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Directly examines GP suspicion, referral behavior, and diagnostic intervals for cancer recurrence in general practice, which maps closely to real primary-care decision-making.
Validity, Bias Control & Precision 4.0
Retrospective cohort with GP survey data and only a 48% response rate, creating substantial risk of selection/nonresponse bias and confounding; precision reporting is limited (few CIs/p-values).
Patient-Oriented Outcomes 4.0
Main outcome is time to recurrence diagnosis (a process/interval measure); no direct reporting of patient-important outcomes such as survival, morbidity, symptoms, or quality of life.
Magnitude of Net Benefit 3.0
Although a 60-day shorter median diagnostic interval is reported when GPs suspected cancer, this is observational and not linked to downstream health outcomes or harms (e.g., over-referral burden).
Implementability & Practicality 6.0
Findings are relatively actionable (emphasizing consideration of recurrence and use of existing fast-track pathways), but the study does not test a specific implementable intervention to change practice.
Practice-Changing Potential 5.0
Provides useful benchmarking and highlights variation by cancer type and the association between suspicion and faster diagnosis, but does not establish causal effects or demonstrate improved patient outcomes.
7. 5.0
Evaluating the role of faecal calprotectin in older adults: a retrospective observational study.
Overall: Primary-care relevant question with practical implications, but the retrospective design and lack of reported diagnostic-performance metrics in the abstract make the clinical impact and reliability hard to judge.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 8.0
Faecal calprotectin is commonly ordered in primary care to guide referral for colonoscopy, and the study specifically targets interpretation in adults ≥50 years—a frequent primary-care scenario.
Validity, Bias Control & Precision 4.0
Retrospective, single-network observational design with likely selection bias (only patients who both had FC and proceeded to colonoscopy); the abstract provides limited quantitative diagnostic-performance data and no precision estimates.
Patient-Oriented Outcomes 3.0
Outcomes are diagnostic accuracy/identification of pathology rather than direct patient outcomes (symptoms, quality of life, morbidity, mortality).
Magnitude of Net Benefit 3.0
The abstract asserts sensitivity and a possible 'rule-out' role but does not report key effect sizes (e.g., sensitivity/specificity, missed cancer/IBD rates, absolute risk changes) or downstream harms/benefits.
Implementability & Practicality 8.0
FC (and FIT where available) are already accessible tests in many primary-care pathways and could be implemented without major new infrastructure, though interpretation in older adults may still be complex.
Practice-Changing Potential 4.0
It challenges guideline caution by suggesting FC may still help rule out disease in older adults with negative FIT, but the evidence presented in the abstract is incomplete and observational, limiting immediate practice change.
8. 4.8
Continuity of primary care and end-of-life care costs in dementia: a retrospective cohort study.
Overall: A highly primary-care-relevant observational study suggesting GP continuity may reduce end-of-life dementia costs, but absent effect sizes and patient-centered outcomes limit confidence and practical impact.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Directly addresses GP continuity and resource use for people with dementia near end of life—an important primary-care-facing population and care-process question.
Validity, Bias Control & Precision 5.0
Large linked-dataset retrospective cohort with multivariable modeling, but nonrandomized design is highly confounding-prone and the abstract omits key quantitative results/precision details.
Patient-Oriented Outcomes 3.0
Focuses on costs (and only suggests admissions), without reporting patient-centered outcomes such as symptom burden, place of death aligned with preferences, caregiver outcomes, or quality of life.
Magnitude of Net Benefit 3.0
States an association with lower total costs, but provides no effect sizes, uncertainty, or trade-offs (e.g., whether reduced utilization affected patient experience), limiting assessment of net benefit.
Implementability & Practicality 5.0
Improving continuity is conceptually actionable in primary care but often requires system-level scheduling, staffing, and access changes; the abstract gives no concrete intervention pathway.
Practice-Changing Potential 4.0
Supports the general rationale for continuity but, given observational design and missing quantitative results, is unlikely to change practice on its own beyond reinforcing existing priorities.
9. 4.7
Incentives and Equity: A Randomized Controlled Trial to Improve Glycemic Control in Socioeconomically Disadvantaged Patients With Diabetes.
Overall: This randomized trial addresses a highly relevant primary-care equity problem, but the abstract lacks key results and focuses on a surrogate outcome (HbA1c), making the net benefit and practice impact uncertain despite a plausible, implementable intervention.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 8.5
Targets uncontrolled type 2 diabetes in socioeconomically disadvantaged community patients—highly relevant to primary care chronic disease management and equity-focused interventions.
Validity, Bias Control & Precision 6.0
Randomized controlled trial with 186 participants supports internal validity, but the abstract provides minimal methodological detail (eg, concealment/blinding/follow-up) and the results reporting is incomplete, limiting confidence and precision.
Patient-Oriented Outcomes 2.0
The outcome referenced is HbA1c (glycemic control), which is a surrogate marker; no patient-important outcomes (complications, hospitalizations, quality of life) are reported.
Magnitude of Net Benefit 2.0
Effect size and comparative results are not actually reported in the provided abstract text, and potential downsides/burdens (administration, unintended effects) are not quantified.
Implementability & Practicality 6.0
A voucher-based conditional copay reduction could be operationalized by health plans/pharmacies, but it requires administrative infrastructure and ongoing monitoring of HbA1c to determine eligibility.
Practice-Changing Potential 3.5
Conceptually important (financial barriers and incentives), but without clearly reported outcome differences or harms, it is difficult to justify changing practice or policy based on this abstract alone.
10. 4.4
Evaluating genotype-treatment interactions for high-risk medications in British general practice: a retrospective cohort study using UK Biobank.
Overall: A primary-care–relevant, large retrospective analysis of pharmacogenetic interactions for serious adverse drug effects, but with limited reported statistical detail and essentially null findings, it offers little actionable or practice-changing guidance.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 8.0
Focuses on high-risk medications prescribed in British general practice and the potential role of pharmacogenetics in routine primary care prescribing decisions.
Validity, Bias Control & Precision 4.0
Large population-based dataset (UK Biobank) is a strength, but the study is retrospective and the abstract provides no effect sizes, confidence intervals, or details on confounding control; authors also note phenotypic imprecision and methodological limitations.
Patient-Oriented Outcomes 7.0
The outcome is medically important adverse drug effects/serious ADEs, which are patient-important events rather than surrogate markers.
Magnitude of Net Benefit 2.0
No statistically significant genotype–treatment interactions were observed, so there is no demonstrated clinical benefit from using the assessed variants to reduce important ADEs.
Implementability & Practicality 3.0
Because the study does not identify actionable genotype–drug pairs, it does not provide a clear implementable approach; applying pharmacogenetics in practice would also require testing and infrastructure not addressed in the abstract.
Practice-Changing Potential 2.5
The negative/neutral findings and lack of actionable results make it unlikely to change prescribing practice based on this abstract alone.
Score Guide: 9-10 Exceptional 7-8 Strong 5-6 Moderate 3-4 Weak 1-2 Poor
Showing top 10 of 14

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