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Kidney International Reports Nov 2023In clinical practice, kidney (dys)function is monitored through creatinine-based estimations of glomerular filtration rate (eGFR: Modification of Diet in Renal Disease...
INTRODUCTION
In clinical practice, kidney (dys)function is monitored through creatinine-based estimations of glomerular filtration rate (eGFR: Modification of Diet in Renal Disease [MDRD], Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). Creatinine is recognized as a late and insensitive biomarker of glomerular filtration rate (GFR). The novel biomarker proenkephalin (PENK) may overcome these limitations, but no PENK-based equation for eGFR is currently available. Therefore, we developed and validated a PENK-based equation to assess GFR.
METHODS
In this international multicenter study in 1354 stable and critically ill patients, GFR was measured (mGFR) through iohexol or iothalamate clearance. A generalized linear model with sigmoidal nonlinear transfer function was used for equation development in the block-randomized development set. Covariates were selected in a data-driven fashion. The novel equation was assessed for bias, precision (mean ± SD), and accuracy (eGFR percentage within ±30% of mGFR, P30) in the validation set and compared with MDRD and CKD-EPI.
RESULTS
Median mGFR was 61 [44-81] ml/min per 1.73 m. In order of importance, PENK, creatinine, and age were included, and sex or race did not improve performance. The PENK-based equation mean ± SD bias of the mGFR was 0.5 ± 15 ml/min per 1.73 m, significantly less compared with MDRD (8 ± 17, < 0.001) and 2009 CKD-EPI (5 ± 17, < 0.001), not reaching statistical significance compared with 2021 CKD-EPI (1.3 ± 16, = 0.06). The P30 accuracy of the PENK-based equation was 83%, significantly higher compared with MDRD (68%, < 0.001) and 2009 CKD-EPI (76%, < 0.001), similar to 2021 CKD-EPI (80%, 0.13).
CONCLUSION
Overall, the PENK-based equation to assess eGFR performed better than most creatinine-based equations without using sex or race.
PubMed: 38025210
DOI: 10.1016/j.ekir.2023.08.006 -
Kidney360 Dec 2023Using multiple markers may improve GFR estimation especially in settings where creatinine and cystatin C are known to be limited. Panel eGFR is a novel multimarker eGFR...
KEY POINTS
Using multiple markers may improve GFR estimation especially in settings where creatinine and cystatin C are known to be limited. Panel eGFR is a novel multimarker eGFR equation consisting of age, sex, cystatin C, and nuclear magnetic resonance–measured creatinine, valine, and myo-inositol. eGFR-Cr and eGFR-Cr-CysC may underestimate measured GFR, while panel eGFR was unbiased among younger Black male individuals.
BACKGROUND
Using multiple markers may improve accuracy in GFR estimation. We sought to externally validate and compare the performance of a novel multimarker eGFR (panel eGFR) equation among Black and White persons using the Genetic Epidemiology Network of Arteriopathy cohort.
METHODS
We included 224 sex, race/ethnicity, and measured GFR (mGFR) category–matched persons, with GFR measured using urinary clearance of iothalamate. We calculated panel eGFR using serum creatinine, valine, myo-inositol, cystatin C, age, and sex. We compared its reliability with current eGFR equations (2021 CKD Epidemiology Collaboration creatinine [eGFR-Cr] and creatinine with cystatin C [eGFR-Cr-CysC]) using median bias, precision, and accuracy metrics. We evaluated each equation's performance in age, sex, and race subgroups.
RESULTS
In the overall cohort, 49% were Black individuals, and mean mGFR was 79 ml/min per 1.73 m. Panel eGFR overestimated mGFR (bias: −2.4 ml/min per 1.73 m; 95% confidence interval [CI], −4.4 to −0.7), eGFR-Cr-CysC underestimated mGFR (bias: 4.8 ml/min per 1.73 m; 95% CI, 2.1 to 6.7), while eGFR-Cr was unbiased (bias: 2.0 ml/min per 1.73 m; 95% CI, −1.1 to 4.6). All equations had comparable accuracy. Among Black male individuals younger than 65 years, both eGFR-Cr (bias: 17.0 ml/min per 1.73 m; 95% CI, 8.6 to 23.5) and eGFR-Cr-CysC (bias: 14.5 ml/min per 1.73 m; 95% CI, 6.0 to 19.7) underestimated mGFR, whereas panel eGFR was unbiased (bias: 1.7 ml/min per 1.73 m; 95% CI, −3.4 to 10.0). Metrics of accuracy for all eGFRs were acceptable in all subgroups except for panel eGFR in Black female individuals younger than 65 years (P30: 73.3%).
CONCLUSIONS
Panel eGFR can be used to estimate mGFR and may have utility among Black male individuals younger than 65 years where current CKD Epidemiology Collaboration equations are biased.
Topics: Kidney Function Tests; Glomerular Filtration Rate
PubMed: 37986202
DOI: 10.34067/KID.0000000000000304 -
Pflugers Archiv : European Journal of... Nov 2023Chronic kidney disease (CKD) is one of the most common chronic diseases worldwide, with increasing rates of morbidity and mortality. Thus, early detection is essential... (Review)
Review
Chronic kidney disease (CKD) is one of the most common chronic diseases worldwide, with increasing rates of morbidity and mortality. Thus, early detection is essential to prevent severe adverse events and the progression of kidney disease to an end stage. Glomerular filtration rate (GFR) is the most appropriate index to evaluate renal function in both clinical practice and basic medical research. Several animal models have been developed to understand renal disease induction and progression. Specifically, murine models are useful to study the pathogenesis of renal damage, so a reliable determination of GFR is essential to evaluate the progression of CKD. However, as in clinical practise, the estimation of GFR in murine by levels of serum/urine creatinine or cystatin-C could not be accurate and needed other more reliable methods. As an alternative, the measurement of GFR by the clearance of exogenous markers like inulin, sinistrin, Cr-EDTA, Tc-DTPA, I-iothalamate, or iohexol could be performed. Nevertheless, both approaches-estimation or measurement of GFR-have their limitations and a standard method for the GFR determination has not been defined. Altogether, in this review, we aim to give an overview of the current methods for GFR assessment in murine models, describing each methodology and focusing on their advantages and limitations.
PubMed: 37552296
DOI: 10.1007/s00424-023-02841-9 -
Bioengineering (Basel, Switzerland) Jun 2023An accurate estimate of glomerular filtration rate (eGFR) is essential for proper clinical management, especially in patients with kidney dysfunction. This prospective...
An accurate estimate of glomerular filtration rate (eGFR) is essential for proper clinical management, especially in patients with kidney dysfunction. This prospective observational study evaluated the real-world performance of the nuclear magnetic resonance (NMR)-based GFR equation, which combines creatinine, cystatin C, valine, and myo-inositol with age and sex. We compared GFR performance to that of the 2021 CKD-EPI creatinine and creatinine-cystatin C equations (CKD-EPI and CKD-EPI), using 115 fresh routine samples of patients scheduled for urinary iothalamate clearance measurement (mGFR). Median bias to mGFR of the three eGFR equations was comparably low, ranging from 0.4 to 2.0 mL/min/1.73 m. GFR outperformed the 2021 CKD-EPI equations in terms of precision (interquartile range to mGFR of 10.5 vs. 17.9 mL/min/1.73 m for GFR vs. CKD-EPI; = 0.01) and accuracy (P15, P20, and P30 of 66.1% vs. 48.7% [ = 0.007], 80.0% vs. 60.0% [ < 0.001] and 95.7% vs. 86.1% [ = 0.006], respectively, for GFR vs. CKD-EPI). Clinical parameters such as etiology, comorbidities, or medications did not significantly alter the performance of the three eGFR equations. Altogether, this study confirmed the utility of GFR for accurate GFR estimation, and its potential value in routine clinical practice for improved medical care.
PubMed: 37370648
DOI: 10.3390/bioengineering10060717