Observational study finds blood test mismatch associated with worsened kidney function and mortality — Evidence Review
Published in Journal of the American Medical Association, by researchers from NYU Langone Health, University of California, San Francisco, Charite-Universitatsmedizin Berlin
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Table of Contents
A major international study suggests that large differences between two common kidney function blood tests—creatinine and cystatin C—may signal higher risks of kidney failure, heart disease, and premature death. Related research broadly supports these findings, with multiple studies indicating that cystatin C provides a more sensitive and accurate assessment of kidney health than creatinine alone, especially in detecting early dysfunction and predicting adverse outcomes (1, 2, 3, 5). For further details, see the original release from NYU Langone Health.
- Multiple meta-analyses and cohort studies consistently report that cystatin C is a superior and more sensitive marker for kidney function compared to creatinine, particularly in early disease stages and among high-risk groups such as people with diabetes or critical illness (1, 3, 5).
- Combining cystatin C and creatinine improves risk stratification and the prediction of mortality and progression to end-stage renal disease, as supported by large population studies and systematic reviews (2, 4).
- The new study's finding that disagreements between the two tests are common in hospitalized or ill patients, and associated with worse outcomes, extends prior evidence by quantifying the prevalence and clinical significance of these discrepancies in a large, diverse international cohort (5).
Study Overview and Key Findings
Chronic kidney disease (CKD) continues to be a growing global health concern, now ranked among the top causes of death worldwide. Accurate measurement of kidney function is essential not only for diagnosing CKD but also for guiding safe and effective medication dosing. Traditionally, clinicians have relied on creatinine-based blood tests, but emerging evidence highlights the value of cystatin C as a complementary biomarker. The recent study from NYU Langone Health stands out as the largest investigation to date analyzing the clinical implications of discrepancies between these two tests, following over 860,000 adults internationally for more than a decade and examining their long-term health outcomes.
| Property | Value |
|---|---|
| Organization | NYU Langone Health, University of California, San Francisco, Charite-Universitatsmedizin Berlin |
| Journal Name | Journal of the American Medical Association |
| Authors | Michelle Estrella, Kai-Uwe Eckardt, Morgan Grams, Josef Coresh, Shoshana Ballew, Yingying Sang, Aditya Surapaneni |
| Population | Adults with kidney function tests |
| Sample Size | 860,966 adults |
| Methods | Observational Study |
| Outcome | Kidney function, heart disease, death risks |
| Results | One third had cystatin C results indicating 30% worse kidney function. |
Literature Review: Related Studies
To place these findings in context, we searched the Consensus paper database, which aggregates over 200 million research articles. The following queries were used to identify relevant literature:
- cystatin C kidney function correlation
- blood test accuracy kidney failure
- kidney failure mortality risk factors
Literature Review Table
| Topic | Key Findings |
|---|---|
| How do cystatin C and creatinine compare in assessing kidney function? | - Cystatin C is generally a more accurate and sensitive marker of kidney function than creatinine, both in general and in specific populations (1, 3, 5). - Combining both markers improves the accuracy of kidney function assessment and risk prediction (2). |
| What is the relationship between kidney function estimates and risks of adverse outcomes? | - Lower kidney function, especially as detected by cystatin C, is associated with increased risk of mortality, cardiovascular events, and kidney failure (2, 11, 12). - Discrepancies between creatinine and cystatin C estimates may signal higher risk (5). |
| How do these tests influence clinical management and drug dosing? | - Cystatin C-based eGFR is more predictive of drug clearance and can better guide dosing, especially when muscle wasting affects creatinine levels (4, 5). - Accurate kidney assessment is vital for adjusting medications and preventing adverse effects (4, 7). |
| What are the broader trends and risk factors in kidney failure and mortality? | - CKD and kidney failure are increasingly common, with rising global mortality, especially among those with diabetes and hypertension (12, 13). - Risk calculators and screening strategies should account for competing mortality risks and early detection (14). |
How do cystatin C and creatinine compare in assessing kidney function?
A broad body of evidence indicates that cystatin C offers improved sensitivity and accuracy compared to creatinine in measuring kidney function. Meta-analyses and observational studies consistently report that cystatin C correlates better with gold-standard GFR measurements, is less affected by factors such as muscle mass, and allows for earlier detection of kidney impairment. These advantages are particularly notable in populations at risk for rapid muscle loss, such as critically ill or diabetic patients (1, 3, 5).
- Cystatin C provides a higher correlation with measured GFR than creatinine, as demonstrated by both correlation coefficients and ROC curve analyses (1, 3).
- In diabetic and critically ill patients, cystatin C detects early kidney dysfunction more reliably than creatinine, which can be confounded by changes in muscle mass (3, 5).
- The superiority of cystatin C is evident in both general and specific patient populations, supporting its use in a wide range of clinical contexts (1, 3).
- The new NYU Langone study quantifies the clinical impact of discordant creatinine and cystatin C results, showing that such discrepancies are common and clinically meaningful (5).
What is the relationship between kidney function estimates and risks of adverse outcomes?
Multiple studies demonstrate that lower kidney function, as estimated by either creatinine or cystatin C, is strongly associated with increased risks of mortality, cardiovascular events, and progression to kidney failure. Importantly, adding cystatin C to creatinine-based risk assessments improves the prediction of these outcomes. The new study extends this by showing that a significant gap between the two tests is itself a marker for higher risk (2, 11, 12, 5).
- Large meta-analyses show that cystatin C-based eGFR is more closely linked to all-cause and cardiovascular mortality than creatinine-based estimates (2).
- Chronic kidney disease, regardless of the biomarker used, is associated with substantially elevated risks of death and cardiovascular disease (11, 12).
- Discrepancies between tests, such as cystatin C indicating significantly worse kidney function than creatinine, identify individuals at particularly high risk (5).
- Early detection of reduced kidney function may allow for timely intervention and risk reduction (2, 11).
How do these tests influence clinical management and drug dosing?
Accurate kidney function measurement is essential for determining safe medication dosing, particularly for drugs with narrow therapeutic windows or renal clearance. Systematic reviews indicate that cystatin C-based eGFR is more predictive of drug pharmacokinetics than creatinine, especially in contexts of muscle wasting or acute illness. This has direct implications for patient safety and treatment efficacy (4, 5, 7).
- Cystatin C-based estimates are more accurate for drug dosing, particularly for medications cleared by the kidneys (4).
- Muscle loss, common in critical illness, can falsely elevate creatinine-based eGFR, making cystatin C a more reliable indicator in these patients (5).
- Clinical guidelines increasingly recommend incorporating cystatin C to optimize medication management and reduce the risk of toxicity or underdosing (4, 7).
- Despite these advantages, cystatin C testing remains underused in routine clinical practice (5).
What are the broader trends and risk factors in kidney failure and mortality?
The global burden of CKD and kidney failure is rising, with increasing numbers of affected individuals and associated deaths. Diabetes, hypertension, and cardiovascular disease are key risk factors for progression and mortality. Recent research also emphasizes the importance of accounting for competing mortality risks in predictive models, and the need for improved early detection and access to care (12, 13, 14).
- CKD is now one of the leading causes of death worldwide, with a disproportionate impact in lower-income regions due to limited access to therapy (12, 13).
- Poorly managed diabetes is a major driver of the increase in kidney failure deaths, highlighting the need for better prevention and early intervention (13).
- Kidney failure risk calculators that ignore the high background risk of mortality may overestimate the risk of progression to end-stage disease (14).
- The new study's findings support a move toward more nuanced risk assessment and earlier identification of at-risk individuals (5, 12).
Future Research Questions
Although recent studies have advanced our understanding of kidney function assessment and its clinical implications, important questions remain. Further research is needed to validate these findings in diverse populations, explore the mechanistic basis for test discrepancies, and evaluate the impact of broader cystatin C testing on patient outcomes and healthcare systems.
| Research Question | Relevance |
|---|---|
| What are the underlying biological causes of discrepancies between creatinine and cystatin C in kidney function tests? | Understanding the mechanisms behind discordant test results could help refine risk prediction and guide targeted interventions (5). |
| Does routine use of cystatin C testing improve clinical outcomes for patients at risk of kidney failure? | Large-scale trials are needed to determine whether adding cystatin C to routine testing leads to earlier intervention and reduced morbidity and mortality (2, 5). |
| How can kidney function tests be optimized for drug dosing in special populations, such as the critically ill? | Individuals with muscle wasting or critical illness are at high risk for inaccurate dosing based on creatinine; improved methods could enhance safety (4, 5). |
| What are the cost-effectiveness and health system impacts of widespread cystatin C testing? | Evaluating the economic and system-level implications will inform policy decisions on implementing routine cystatin C measurement (5). |
| How do test discrepancies affect long-term risk stratification in diverse ethnic and age groups? | Validation in varied populations will help ensure that risk prediction models are equitable and effective for all patients (2, 13). |