Performance of Creatinine-Based Estimates of GFR in Kidney Transplant Recipients: A Systematic Review

doi:10.1053/j.ajkd.2008.02.308

American Journal of Kidney Diseases

Volume 51, Issue 6, June 2008, Pages 1005-1015

https://doi.org/10.1053/j.ajkd.2008.02.308 Get rights and content

Background

Glomerular filtration rate (GFR) commonly is estimated in kidney transplantation by using creatinine-based estimation equations. The performance of these equations in kidney transplant recipients is unclear, with conflicting results between studies.

Study Design

Systematic review.

Setting & Population

Stable adult kidney transplant recipients more than 6 months posttransplantation.

Selection Criteria

Reporting of or ability to calculate from available data the GFR estimation equation bias (mean difference between measured GFR and estimated GFR) and percent accuracy (percentage of GFR estimates within 10%, 20%, or 30% of measured GFR).

Index Tests

Creatinine-based GFR estimation equations (Cockcroft-Gault, 6-variable Modification of Diet in Renal Disease [MDRD] Study, 4-variable MDRD Study, and Nankivell).

Reference Tests

GFR determination using plasma or renal clearance of inulin, radioisotopes, or nonradiographic contrast.

Results

The search yielded 23 studies. For the 4-variable MDRD Study equation, bias ranged from −11.4 to +9.2 mL/min/1.73 m² (0.15 mL/s/1.73 m²). Only 76% of estimates were within 30% of measured GFR. For the Cockcroft-Gault equation, bias ranged from −4.0 to +16 mL/min/1.73 m² and 73% of estimates were within 30% of measured GFR. For the Nankivell equation, bias ranged from −1.4 mL/min to 36.3 mL/min with a 30% accuracy of only 68%.

Limitations

This review is limited by the inability to pool bias data, lack of calibration of serum creatinine in the majority of studies, and inclusion of nonindependent observations in many studies.

Conclusions

Differences in patient populations, baseline GFRs of the study group, reference standard GFR used, and creatinine assay calibration likely account for the heterogeneity in results. These factors need to be considered by investigators and clinicians when interpreting estimates of GFR in kidney transplant recipients.

Section snippets

Search Strategy

A systematic literature search was performed using the MEDLINE (1966 to October 2006) and EMBASE (1980 to October 2006) databases with the assistance of a librarian with expertise in electronic searches. In MEDLINE, the medical subject heading (MeSH) term “kidney transplantation” was combined with Cockcroft-Gault formula or creatinine-based equations or Nankivell or MDRD or Modification of Diet in Renal Disease. In EMBASE, the MeSH term “kidney transplantation” was combined with the MeSH term

Results

The search yielded 692 citations from MEDLINE, 569 citations from EMBASE, and 14 from the hand search (Fig 1). Of 1,275 citations, 68 were considered potentially eligible. Full-text evaluation identified 23 studies that met inclusion criteria.3, 7, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 The most common reason for exclusion was failure to report an estimate of GFR (Fig 1).

Discussion

This study shows the wide range of bias and accuracy values that exist between studies with both overestimation and underestimation of measured GFR using creatinine-based estimation equations. The between-study heterogeneity likely is caused by 3 main factors. First, there are reported and likely some unreported differences in the populations studied. Race, with its known relationship to serum creatinine,⁶ was not reported in most studies. Of studies that reported race, the overwhelming

Acknowledgements

Support: None.

Financial Disclosure: None.

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Cited by (93)

Do We Need a New Creatinine-Based Estimated GFR Equation for Kidney Transplant Recipients?
2024, American Journal of Kidney Diseases
β-Trace Protein and β2-Microglobulin do not Improve Estimation of Glomerular Filtration Rate in Kidney Transplant Recipients Compared With Creatinine and Cystatin C
2023, Transplantation Proceedings
Reliable estimates of glomerular filtration rate (eGFR) are important for detecting changes in graft function in kidney transplant recipients. Current eGFR equations are based on plasma creatinine and/or cystatin C; however, these are associated with significant bias. This study investigated if equations based on β-trace protein (BTP) and β2-microglobulin (B2M) performed better than the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on creatinine and cystatin C among kidney transplant recipients.
We included samples and data from the clinical trial CONTEXT. Glomerular filtration rate (GFR) was measured by plasma clearance of an exogenous marker. The eGFR was calculated using the CKD-EPI equations for estimating GFR from BTP and/or B2M and the 2021 CKD-EPI creatinine and creatinine-cystatin C equations. The GFR estimates were evaluated 3 (n = 82) and 12 (n = 64) months after transplant using mean bias, precision, and accuracy. Furthermore, we analyzed the ability of the equations to correctly classify the direction of changes in measured GFR from 3 to 12 months.
Among the BTP- and B2M-based equations, the combined eGFR-BTP-B2M performed best with respect to precision (SD = 7.64 mL/min/1.73 m²) and accuracy (±10% from measured GFR = 36%). The eGFR-BTP-B2M and the eGFR-creatinine-cystatin C (2021) performed similarly when comparing precision, accuracy, and residuals (P = .481). The BTP- and/or B2M-based equations did not perform better than the eGFR-creatinine-cystatin C (2021) in correctly classifying the direction of changes in measured GFR from 3 to 12 months.
β-trace protein and/or B2M do not improve the estimation of GFR when compared with creatinine- and cystatin C-based 2021 CKD-EPI equations.
Prediction of worsening postoperative renal function in older candidates to elective cardiac surgery: Choosing the best eGFR formula may not be enough
2023, Heart and Lung
Though renal impairment is highly prevalent in older patients and influence post-operative outcomes in cardiac surgery; its prognostic relevance is debated and not fully assessed by surgical risk scores.
We investigated the predictive role of estimated glomerular filtration rate formulas for in-hospital worsening renal function (WRF) after cardiac surgery.
We prospectively enrolled in single-center cohort study, patients aged ≥ 75 years candidate to elective cardiac surgery. Four creatinine-based equations were used to calculate estimated glomerular filtration rate (eGFR) formulas: Cockroft-Gault, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology, and Berlin Initiative Study 1 formulas. Each patient underwent geriatric and clinical evaluation before surgery with calculation of the Society of Thoracic Surgeons scores. In-hospital WRF was defined as a composite of an increase in SCr ≥0.5 mg/dl or the occurrence of grade III KDIGO acute kidney injury. The association between each eGFR equation, alone and in models including clinical variables, and WRF was analyzed using logistic regressions and ROC analysis.
WRF occurred in 69 patients (19.8%), and the predictors of WRF were previous acute myocardial infarction, hypertension, 4-mt gait speed performance, and preoperative eGFR, irrespective of the equation used. With all equations, inclusion of these additional variables in the logistic regression models improved the prediction of WRF (AUCs 0.798–0.810).
An accurate assessment of renal function and of physical performance should be incorporated into cardiac surgery risk scores to improve prediction of in-hospital WRF and, hence, risk stratification in older adults undergoing elective cardiac surgery.
Extended Literature Review of the role of erythropoietin stimulating agents (ESA) use in the management of post renal transplant anaemia
2022, Transplantation Reports
: Anemia is known to impact quality of life and survival in both renal and non-renal patients. End stage kidney disease (ESKD) patient's survival substantially improves post transplantation. Observational studies have reported better patients and graft outcomes in non anemic renal transplant recipients. Anemia of chronic kidney disease (CKD) is frequently linked to erythropoietin deficiency. Patients with post-transplant anemia (PTA) represent a distinct subset of CKD population. The benefit of using erythropoietin stimulating agents (ESA) in PTA is not clearly defined.
: The aim of this extended literature review is to define the role of ESA use in improving hemoglobin (Hb) level and graft survival in patients with PTA.
: An extended literature review was done to identify randomized controlled trials (RCTs) with patients with PTA as the study population, the use of erythropoietin stimulating agents as the intervention, and the renal function and Hb level as the outcomes. The aim of this literature review is to delineate the role of using ESA in PTA. Medline, Google scholar, Scopus, and CINHAL data bases were searched and papers meeting the pre-set inclusion criteria were identified.
: A total of 163 papers were identified. After screening the results, four papers met the inclusion criteria and were included for review. 2/4 papers recruited patients with early PTA, while 2/4 papers recruited patients with late PTA. The early PTA papers were not consistent in reporting the effect of ESA in improving renal outcomes. Both studies showed that using ESA had no additional benefit in anemia treatment. 2/4 studies looked at late PTA. The study designs were similar and the follow up period was 2-3 years. Both studies showed a better graft survival in the higher Hb group.
: In the case of early PTA, the benefit of using ESA is not clear. The two RCTs studying the effect of ESA in patients with late PTA showed that targeting higher Hb levels was associated with better graft function. The optimal Hb target and the utility of intravenous iron need further clarifications.
Performance of the 2021 Race-Free CKD-EPI Creatinine- and Cystatin C–Based Estimated GFR Equations Among Kidney Transplant Recipients
2022, American Journal of Kidney Diseases
Citation Excerpt :
The dataset used to develop the new eGFR equations did not report the inclusion of KTRs.8 Validation of eGFR equations among KTRs is critical because previous eGFR equations have demonstrated low accuracy and poor precision among KTRs, often leading to misclassification of CKD staging.12,13 In the present study, we found overall similar performance of the new 2021 CKD-EPI eGFR equations compared with the 2009/2012 CKD-EPI equations among the kidney transplant population.
Race-free estimated glomerular filtration rate (eGFR) equations incorporating creatinine with and without cystatin C were recently developed and recommended for routine use. However, the performance of these equations among kidney transplant recipients (KTRs) remains unknown.
Cross-sectional study to validate the 2021 race-free Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) eGFR equation based on creatinine alone (eGFR_cr) or based on creatinine and cystatin C (eGFR_cr-cys) among KTRs.
KTRs in stable condition (N = 415) from Canada and New Zealand with same-day measurements of creatinine, cystatin C, and glomerular filtration rate (GFR) using radiolabeled diethylenetriaminepentaacetic acid.
The 2009 CKD-EPI eGFR_cr, 2021 CKD-EPI eGFR_cr, 2012 CKD-EPI eGFR_cr-cys, 2021 CKD-EPI eGFR_cr-cys, 2012 CKD-EPI eGFR_cys, and Modification of Diet in Renal Disease (MDRD) Study eGFR equations were compared with measured GFR.
Bias, precision, accuracy, and correct classification by CKD stage. Bias was defined as the difference between estimated and measured GFR. Precision was represented by the interquartile range. Accuracy was defined as the percentages of participants with eGFRs within 10%/20%/30% (P₁₀/P₂₀/P₃₀) of measured GFR, root mean square error, and mean absolute error.
87% of patients studied were White, 3% Black, and 10% other races. Mean measured GFR was 53 ± 19 (SD) mL/min/1.73 m². The 2009 and 2021 CKD-EPI eGFR_cr equations demonstrated similar median bias (−2.3 vs −0.2 mL/min/1.73 m², respectively), precision (14.5 vs 14.9 mL/min/1.73 m²), and accuracy (P₁₀/P₂₀/P₃₀, 32%/65%/84% vs 33%/63%/84%). The 2012 and 2021 CKD-EPI eGFR_cr-cys equations also demonstrated similar median bias (−3.6 vs 0.3 mL/min/1.73 m², respectively), precision (13.3 vs 14.3 mL/min/1.73 m²), and accuracy (P₁₀/P₂₀/P₃₀, 32%/63%/80% vs 32%/67%/83%). No clear difference in performance was detected between the 2021 CKD-EPI eGFR_cr and eGFR_cr-cys equations among KTRs. The proportion of correct classification by CKD stage was similar across all eGFR equations.
Moderate sample size, few patients had a GFR <30 mL/min/1.73 m², and the large majority of patients were White.
Among KTRs, the 2021 race-free CKD-EPI eGFR equations perform similarly to the previous CKD-EPI equations that included race correction terms. No significant difference in performance was observed between the 2021 CKD-EPI eGFR_cr and eGFR_cr-cys equations in the kidney transplant population.
Simultaneous glomerular filtration rate determination using inulin, iohexol, and <sup>99m</sup>Tc-DTPA demonstrates the need for customized measurement protocols
2021, Kidney International
Urinary inulin clearance is considered the gold standard of glomerular filtration rate (GFR) measurement but plasma clearance of less expensive and more accessible tracers is more commonly performed. Many plasma sampling protocols exist but little is known about their accuracy. Here, the study objectives were to compare plasma iohexol and ^99mTc-DTPA GFR with varying sampling strategies to the GFR measured by urinary inulin and to identify protocols with the greatest accuracy according to clinical characteristics. GFR was measured simultaneously using urinary inulin, plasma iohexol, and plasma ^99mTc DTPA clearance. Blood was sampled from 2 to 10 hours after injection. For each method, bias, precision, and accuracy (P30 and mean absolute error) were calculated for the entire cohort and for eGFR-EPI creatinine subgroups (<30, 30–59, and ≥60 ml/min/1.73m²) and the edema stage using urinary inulin clearance as the gold standard. The mean inulin GFR of the 77 participants was 33 ml/min/1.73m². Delay of both the initial and the final samples in plasma iohexol protocols yielded the highest accuracy in the setting of low GFR (<30 ml/min/1.73m²). Early initial and final samples yielded the highest accuracy in the setting of high GFRs (≥60 ml/min/1.73m²). No sampling strategy was accurate in edematous patients. Thus, our study demonstrates that customization of GFR protocols according to the anticipated level of GFR are required to optimize protocol accuracy.

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: Originally published online as doi:10.1053/j.ajkd.2008.02.308 on May 2, 2008.

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Original InvestigationTransplantationPerformance of Creatinine-Based Estimates of GFR in Kidney Transplant Recipients: A Systematic Review

Background

Study Design

Setting & Population

Selection Criteria

Index Tests

Reference Tests

Results

Limitations

Conclusions

Section snippets

Search Strategy

Results

Discussion

Acknowledgements

Kidney Int

Kidney Int

Am J Transplant

J Urol

Am J Transplant

Transplant Proc

Am J Transplant

Kidney Int

Am J Transplant

Am J Transplant

Clin Chim Acta

Kidney Int

Kidney Int

Am J Transplant

Am J Kidney Dis

Am J Kidney Dis

J Urol

National Kidney Foundation practice guidelines for chronic kidney disease: Evaluation, classification and stratification

Ann Intern Med

Prediction of creatinine clearance from serum creatinine

Nephron

A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equationModification of Diet in Renal Disease Study Group

Ann Intern Med

Predicting glomerular filtration rate after kidney transplantation

Transplantation

Predictive performance of renal function equations for patients with chronic kidney disease and normal serum creatinine levels

J Am Soc Nephrol

Using serum creatinine to estimate glomerular filtration rate: Accuracy in good health and in chronic kidney disease

Ann Intern Med

Calculation of glomerular filtration rate based on cystatin C in cirrhotic patients

Nephrol Dial Transplant

Original Investigation
Transplantation
Performance of Creatinine-Based Estimates of GFR in Kidney Transplant Recipients: A Systematic Review