Estimated Glomerular Filtration Rate Research Articles

Kidney Measurement and Glomerular Filtration Rate Evolution in Children with Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron, and over time the cystic dilatation leads to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts leads to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and hematuria. However, the presentation of ADPKD varies in children, from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by a mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end-stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra-normal kidney function, we explored the glomerular filtration rates dynamics and the renal ultrasound-adjusted percentiles. In total, 14 out of 16 patients had kidney percentiles over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 mL/min/1.73 m2 when compared to Schwartz eGFR 126.28 ± 33.07 mL/min/1.73 m2, p = 0.14). Also, when the quadratic equation was employed, not even a single patient reached the glomerular hyperfiltration threshold. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1 year of follow-up (quadratic ΔeGFR = −0.32 ± 5.78 mL/min/1.73 m2), as opposed to the Schwartz formula that can falsely classify children in a hyperfiltration state (ΔeGFR = 7.51 ± 19.46 mL/min/1.73 m2), p = 0.019.

Estimating eGFR using serum creatinine or cystatin C in healthy Vietnamese population.

Very few studies worldwide have assessed the estimated glomerular filtration rate (eGFR) using serum cystatin C (ScysC) in comparison to the gold standard measured glomerular filtration rate (mGFR) with a gamma camera technique using 99m-Technetium-Diethylene Triaminepentoacetic Acid (99mTc-DTPA). To determine the eGFR formula with the most accurate estimate of glomerular filtration rate when compared with mGFR in a healthy population in Vietnam. We conducted a cross-sectional descriptive study of more than 100 adults without hypertension. The study subjects were examined for general characteristics and blood biochemistry tests to assess eGFR, and the glomerular filtration rate was measured using 99mTc-DTPA with the Gates technique to record mGFR. The estimated values of the eGFR formula were evaluated and compared with the actual mGFR using 99mTechnetium-DTPA. Serum creatinine (Scr) concentration showed a significant difference between males and females: 0.9 ± 0.1 versus 0.8 ± 0.1 (P < .001), while ScysC concentration did not show this difference. The mGFR in the age groups < 40, 40 to 59, and ≥ 60: 105.0 ± 9.9, 94.8 ± 8.6, and 93.4 ± 10.6, respectively (P < .001). The eGFR-CKD-EPI-cystatin C 2012 formula showed the highest positive correlation with mGFR (ΔGFR = -1.6, R = 0.68, P < .001). eGFR calculated using cystatin C does not require sex adjustment, whereas, for creatinine, sex adjustment is necessary. The eGFR-CKD-Epi-CysC formula showed the lowest difference and a strong correlation with mGFR.

Estimation of glomerular filtration rate with cystatin C in the evaluation of cardiovascular risk

Estimation of glomerular filtration rate with cystatin C in the evaluation of cardiovascular risk

The correlation between pentraxin-3, matrix metalloproteinase-9, and estimated glomerular filtration rate in patients with chronic kidney disease

Background: Chronic kidney disease (CKD) is diagnosed when there is a sustained decrease in the estimated glomerular filtration rate (EGFR) over a period of more than 3 months. While Pentraxin-3 (PTX-3) and Matrix Metalloproteinase-9 (MMP-9) levels increase during the acute phase of the kidney injury, chronic conditions often exhibit alteration in the epithelial mesenchymal transition (EMT).Objectives: This study aimed to elucidate the correlation between serum PTX-3, MMP-9, and eGFR in patients with CKD. Method: Thirty hypertensive patients with CKD stages 3, 4, and 5, aged between 16 and 65 years, were enrolled in the study (15 males and 15 females). Diagnosis of CKD was based on the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria, utilizing serum creatinine, and CKD-epidemiology Collaboration (CKD-EPI) estimates. Subsequently, serum MMP-9 and PTX-3 levels were quantified. Result: Patients with CKD exhibited significantly higher serum levels of PTX3 and MMP9. Furthermore. a significant negative connection between PTX-3, MMP-9, and EGFR was observed. Additionally, CKD patients displayed a correlation between PTX-3 and MMP-9 concentrations.Conclusion: Plasma levels of PTX-3 and MMP-9 serve as unique, promising, and important markers that contribute to the pathogenesis of CKD.

Utility of Cystatin C-based Equation for the Estimation of Glomerular Filtration Rate in a Pediatric Population.

The accurate assessment of kidney function is vital for the early detection of kidney damage. The estimated glomerular filtration rate GFR (eGFR) from serum cystatin C (CysC) and creatinine-based equations are commonly used in clinical practice as an alternative to the invasive measured glomerular filtration rate (mGFR), which is the usually accepted overall best index of kidney function in health and disease. Recently the CKiD under 25 (CkiD U25) equations have been shown to perform well in children and young adults with chronic kidney disease (CKD). In this focused report, we evaluated the performance of the CkiD U25 equations alongside 3 non-race-corrected (NRC) eGFR equations commonly used in pediatrics in our cohort. mGFR measured following the intravenous injection of tracer Tc-99mDTPA was retrospectively compared with eGFR from these equations in 57 patients (6 months to 22 years) from different races/ethnicities. Ordinary least squares regression analyses were used to assess correlation between the mGFRs and eGFRs. The average mGFR for this cohort was 84.1 mL/min/1.73 m2. The NRC creatinine equations overestimated eGFR across all groups, with the lowest bias for CKiD U25-creatinine (22.59 mL/min/1.73 m2). The best correlations to mGFR, P30, and lowest biases were the CKiD U25-CysC (0.6281, 80.7%, 3.72 mL/min/1.73 m2) and Schwartz CysC (0.6372, 77.2%, -4.68 mL/min/1.73 m2). Overall, both CKiD U25-CysC and Schwartz CysC provide a good estimation of mGFR with the CKiD U25-CysC having the overall best performance compared to mGFR in our study.

Consistency of metabolite associations with measured glomerular filtration rate in children and adults

Abstract Background and hypothesis There is interest in identifying novel filtration markers that lead to more accurate GFR estimates than current markers (creatinine and cystatin C) and are more consistent across demographic groups. We hypothesize that large-scale metabolomics can identify serum metabolites that are strongly influenced by glomerular filtration rate (GFR) and are more consistent across demographic variables than creatinine, which would be promising filtration markers for future investigation. Methods We evaluated the consistency of associations between measured GFR (mGFR) and 887 common, known metabolites quantified by an untargeted chromatography and spectroscopy-based metabolomics platform (Metabolon) performed on frozen blood samples from 580 participants in Chronic Kidney Disease in Children (CKiD), 674 participants in Modification of Diet in Renal Disease (MDRD) Study, and 962 participants in African American Study of Kidney Disease and Hypertension (AASK). We evaluated metabolite-mGFR correlation association with metabolite class, molecular weight, assay platform, and measurement coefficient of variation (CV). Among metabolites with strong negative correlations with mGFR (r &amp;lt; −0.5), we assessed additional variation by age (height in children), sex, race, and BMI. Results A total of 561 metabolites (63%) were negatively correlated with mGFR. Correlations with mGFR were highly consistent across study, sex, race, and BMI categories (correlation of metabolite-mGFR correlations between 0.88 and 0.95). Amino acids, carbohydrates, and nucleotides were more often negatively correlated with mGFR compared to lipids, but there was no association with metabolite molecular weight, LC/MS platform, and measurement CV. Among 114 metabolites with strong negative associations with mGFR (r&amp;lt;−0.5), 27 were consistently not associated with age (height in children), sex, or race. Conclusions The majority of metabolite-mGFR correlations were negative and consistent across sex, race, BMI, and study. Metabolites with consistent strong negative correlations with mGFR and non-association with demographic variables may represent candidate markers to improve estimation of GFR.

Application of improved glomerular filtration rate estimation by a neural network model in patients with neurogenic lower urinary tract dysfunction.

Previous studies have indicated that creatinine (Cr)-based glomerular filtration rate (GFR) estimating equations - including the new Chronic Kidney Disease Epidemiology creatinine (CKD-EPIcr) equation without race and the estimated glomerular filtration rate (eGFR) equation developed for the Chinese population - displayed suboptimal performance in patients with neurogenic lower urinary tract dysfunction (NLUTD), which limited their clinical application for detecting changes in GFR levels in all cohorts. To develop a neural network model based on multilayer perceptron (MLP) for evaluating GFR in Chinese NLUTD patients, and compare the diagnostic performance with Cr-based multiple linear regression equations for Chinese and the CKD-EPIcr equation without race. Single-center, cross-sectional study of GFR estimation from serum Cr, demographic data, and clinical characteristics in Chinese patients with NLUTD. A total of 204 NLUTD patients, from 27 different geographic regions of China, were selected. A random sample of 141 of these subjects was included in the training sample set, and the remaining 63 patients were included in the testing sample set. The reference GFR (rGFR) was assessed by the technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) double plasma sample method. A neural network model based on MLP was developed to evaluate GFR in the training sample set, which was then validated in the testing sample set and compared with Cr-based GFR equations. The MLP-based model showed significant performance improvement in evaluating the difference, absolute difference, precision, and accuracy of GFR estimation compared with the Cr-based GFR equations. Additionally, compared with the rGFR, we found that the MLP-based model provided an acceptable level of accuracy (greater than 85%, which was within a 30% deviation from the rGFR). The MLP-based model offered significant advantages in estimating GFR in Chinese NLUTD patients, and its application could be suggested in clinical practice.

Application of the European Kidney Function Consortium Equation to Estimate Glomerular Filtration Rate: A Comparison Study of the CKiD and CKD-EPI Equations Using the Korea National Health and Nutrition Examination Survey (KNHANES 2008-2021).

Background and Objectives: The European Kidney Function Consortium (EKFC) equation has been newly proposed for estimating glomerular filtration rate (eGFR) across the spectrum of age. We compared the EKFC equation with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in a large-scale Korean population. Materials and Methods: Using the representative Korean health examination data, the Korea National Health and Nutrition Examination Survey (KNHANES 2008-2021), the records of 91,928 subjects (including 9917 children) were analyzed. We compared the EKFC equation with CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations and investigated their agreement across GFR categories. Results: In the total population, the CKD-EPI 2021 equation yielded the highest eGFR value, followed by the CKD-EPI 2009 and EKFC equations. In children, the distribution of eGFR differed significantly between the EKFC and CKiD equations (p < 0.001), with a wider range of eGFR values found with the CKiD equation. Each equation showed weak or moderate agreement on the frequency of the GFR category (κ = 0.54 between EKFC and CKD-EPI 2021; κ = 0.77 between EKFC and CKD-EPI 2009). The eGFR values found by the EKFC equation showed high or very high correlations with those by the CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations (r = 0.85, 0.97, and 0.97, respectively). As eGFR values increased, bigger differences were observed between equations. Conclusions: This large-scale study demonstrates that the EKFC equation would be applicable across the entire age spectrum in Asian populations. It also underscores that national kidney health would be highly affected by an eGFR equation being implemented. Additional investigation and more caution would be warranted for the transition of eGFR equations.

Prevalence of impaired renal function among childless men as compared to fathers: a population-based study

Male reproductive impairment has been linked with an increased risk of numerous non-communicable diseases. Yet, epidemiological data on renal disease among subfertile men is scarce. Therefore, by using male childlessness as a proxy for male infertility, we aimed to investigate its association with renal function. Data was sourced from a population-based cohort including 22,444 men. After exclusion of men aged < 45 years (n = 10,842), the remaining men were divided into two groups: these being childless (n = 5494) and fathers (n = 6108). Logistic regression was applied to explore the association between male childlessness and renal impairment. Childless men as compared to fathers, were more likely to have an estimated-glomerular filtration rate < 60 ml/min/1.73m2 (OR 1.36, 95 CI 1.08–1.70; p = 0.008). After adjustment for age, marital status, smoking habits, diabetes, hypertension and other components of metabolic syndrome, childless men were also more likely to have dipstick proteinuria (OR 1.85, 95 CI 1.16–2.95; p = 0.01). With the growing panorama of disease associated with male reproductive impairment, men with fertility issues may constitute a target population with potential benefit from closer follow-up of their renal function.

Pre-donation Assessment of Cystatin C to Improve Prediction of Pre- and Post-Donation GFR in Potential Living Kidney Donors.

Accurate estimation of glomerular filtration rate (GFR) is crucial in living kidney donation. While most eGFR equations are based on plasma creatinine, its levels are strongly influenced by muscle mass. Application of cystatin C (CysC)-based estimates before donation may improve both estimation of current GFR and prediction of post-donation GFR. We assessed the performance of CKD-EPI equations based on creatinine (eGFRcreat-2009, eGFRcreat-2021), cystatin C (eGFRCysC-2012), or both (eGFRcombined-2012, eGFRcombined-2021) for estimating pre- and post-donation measured GFR in 486 living kidney donors. We subsequently focused on a subgroup of individuals with high/low muscle mass (25% highest/lowest 24-hour urinary creatinine excretion, sex-stratified and height-indexed). Pre-donation eGFRcombined 2012 and eGFRcombined 2021 showed the strongest associations with pre- and post-donation mGFR. Pre-donation eGFRcombined 2021 was most accurate for estimating both pre-donation (bias 0.01±11.9 mL/min/1.73m2) and post-donation mGFR (bias 1.3±8.5 mL/min/1.73 m2). In donors with high/low muscle mass, CysC-based equations (with or without creatinine) performed better compared to equations based on only creatinine. In conclusion, combined eGFR equations yielded a better estimate of pre- and post-donation mGFR, compared to estimates based on creatinine or CysC only. The added value of CysC seems particularly pronounced in donors with high or low muscle mass.

Bias and Accuracy of Glomerular Filtration Rate Estimating Equations in the US

There is increasing concern that continued use of a glomerular filtration rate (GFR) estimating equation adjusted for a single racial group could exacerbate chronic kidney disease-related disparities and inequalities. To assess the performance of GFR estimating equations across varied patient populations. PubMed, Embase, Web of Science, ClinicalTrials.gov, and Scopus databases were systematically searched from January 2012 to February 2023. Inclusion criteria were studies that compared measured GFR with estimated GFR in adults using established reference standards and methods. A total of 6663 studies were initially identified for screening and review. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 2 authors independently extracted data on studies that examined the bias and accuracy of GFR estimating equations. For each outcome, a random-effects model was used to calculate pooled estimates. Data analysis was conducted from March to December 2023. The primary outcomes were bias and accuracy of estimated GFRs in Black vs non-Black patients, as well as in individuals with chronic conditions. Bias was defined as the median difference between the measured GFR and the estimated GFR. Accuracy was assessed with P30 (the proportion of persons in a data set whose estimated GFR values were within 30% of measured GFR values) and measures of heterogeneity. A total of 12 studies with a combined 44 721 patients were included. Significant heterogeneity was found in the bias of various GFR estimation equations. Race-corrected equations and creatinine-based equations tended to overestimate GFR in Black populations and showed mixed results in non-Black populations. For creatinine-based equations, the mean bias in subgroup analysis was 2.1 mL/min/1.73 m2 (95% CI, -0.2 mL/min/1.73 m2 to 4.4 mL/min/1.73 m2) in Black persons and 1.3 mL/min/1.73 m2 (95% CI, 0.0 mL/min/1.73 m2 to 2.5 mL/min/1.73 m2) in non-Black persons. Equations using only cystatin C had small biases. Regarding accuracy, heterogeneity was high in both groups. The overall P30 was 84.5% in Black persons and 87.8% in non-Black persons. Creatinine-based equations were more accurate in non-Black persons than in Black persons. For creatinine-cystatin C equations, the P30 was higher in non-Black persons. There was no significant P30 difference in cystatin C-only equations between the 2 groups. In patients with chronic conditions, P30 values were generally less than 85%, and the biases varied widely. This systematic review and meta-analysis of GFR estimating equations suggests that there is bias in race-based GFR estimating equations, which exacerbates kidney disease disparities. Development of a GFR equation independent of race is a crucial starting point, but not the sole solution. Addressing the disproportionate burden of kidney failure on Black individuals in the US requires an enduring, multifaceted approach that should include improving diagnostics, tackling social determinants of health, confronting systemic racism, and using effective disease prevention and management strategies.

Comparison of estimated GFR using cystatin C versus creatinine in pediatric kidney transplant recipients.

An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. Bias was small with Gentian CysC (0.1ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.

Refining GFR estimation: a quest for the unobservable truth?

Assessing glomerular filtration rate (GFR), which is central to evaluating kidney health, remains challenging. Measured GFR is not widely available and lacks standardization. Estimated GFR can be highly inaccurate for some patients and has limited applicability to many patient populations, such as those who are acutely ill. Recent metabolomic advances show promise for identifying new filtration markers that might enhance GFR estimation. Improving GFR assessment will require refinement in both GFR measurement and estimation methods.

Alternative creatinine-based GFR estimates in United States populations—similar performance, same gaps—is it time to move on?

This study evaluated performance of the European Kidney Function Consortium (EKFC) equation in a US cohort, comparing population-specific (EKFCPS) with race-free (EKFCRF) Q values (median normal creatinine). Both EKFCPS and EKFCRF equations showed less bias than the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation. The percentage of estimated glomerular filtration rate (GFR) within 30% of measured GFR was similar for CKD-EPI 2021 (79.2% [range, 78.5%-79.9%]) and EKFCRF (80.1% [range, 79.4%-80.7%]) equations but improved with the EKFCPS equation (81.1% [range, 80.5%-81.8%]), confirming utility of the EKFC equation in US populations.

Toward Equitable Kidney Function Estimation in Critical Care Practice. Guidance From the Society of Critical Care Medicine's Diversity, Equity, and Inclusion in Renal Clinical Practice Task Force.

Accurate glomerular filtration rate (GFR) assessment is essential in critically ill patients. GFR is often estimated using creatinine-based equations, which require surrogates for muscle mass such as age and sex. Race has also been included in GFR equations, based on the assumption that Black individuals have genetically determined higher muscle mass. However, race-based GFR estimation has been questioned with the recognition that race is a poor surrogate for genetic ancestry, and racial health disparities are driven largely by socioeconomic factors. The American Society of Nephrology and the National Kidney Foundation (ASN/NKF) recommend widespread adoption of new "race-free" creatinine equations, and increased use of cystatin C as a race-agnostic GFR biomarker. Literature review and expert consensus. English language publications evaluating GFR assessment and racial disparities. We provide an overview of the ASN/NKF recommendations. We then apply an Implementation science methodology to identify facilitators and barriers to implementation of the ASN/NKF recommendations into critical care settings and identify evidence-based implementation strategies. Last, we highlight research priorities for advancing GFR estimation in critically ill patients. Implementation of the new creatinine-based GFR equation is facilitated by low cost and relative ease of incorporation into electronic health records. The key barrier to implementation is a lack of direct evidence in critically ill patients. Additional barriers to implementing cystatin C-based GFR estimation include higher cost and lack of test availability in most laboratories. Further, cystatin C concentrations are influenced by inflammation, which complicates interpretation. The lack of direct evidence in critically ill patients is a key barrier to broad implementation of newly developed "race-free" GFR equations. Additional research evaluating GFR equations in critically ill patients and novel approaches to dynamic kidney function estimation is required to advance equitable GFR assessment in this vulnerable population.

New race-free creatinine- and cystatin C-based equations for the estimation of glomerular filtration rate and association with cardiovascular mortality in the AtheroGene study

Renal function is associated with cardiovascular outcomes and mortality. Among equations used to eGFR, CKD–EPI equations show more accurate association with cardiovascular risk and mortality than MDRD. Recently, new CKD–EPI equations were proposed which do not include race and would be considered sufficiently accurate to estimate eGFR in clinical practice. It is unknown if these new race-free equations are comparably well associated with cardiovascular outcomes in high-risk individuals. The analysis was performed in the AtheroGene Study cohort including patients at high cardiovascular risk. eGFR was determined using the established as well as the recently developed formulas which are calculated without the otherwise existing coefficient for black race. The outcome was cardiovascular death. Analyses included Cox-proportional hazard regression and area-under-the-curve calculation. The analysis included 2089 patients followed up for a median of 3.8 years with a maximum of 6.9 years, corresponding to an overall period of 7701 patient-years. Cardiovascular death occurred in 93 (4.45%), corresponding to an annualized rate of 1.2/100 person-years. In all Cox regression analyses, the estimated adjusted GFR was an independent predictor of cardiovascular death. The equations which included cystatin C showed higher C-index compared to those which did not include cystatin C (0.75–0.76 vs. 0.71, respectively). The equations for the estimation of eGFR which include cystatin C are better associated with cardiovascular death compared to the race-free equations which include only creatinine. This finding adds on the related literature which supports the elimination of race in GFR-estimating equations, and promotion of the use of cystatin C.

Evaluation of risk stratification for acute kidney injury: a comparative analysis of EKFC, 2009 and 2021 CKD-EPI glomerular filtration estimating equations.

The adoption of the 2021 CKD-EPIcr equation for glomerular filtration rate (GFR) estimation provided a race-free eGFR calculation. However, the discriminative performance for AKI risk has been rarely validated. We aimed to evaluate the differences in acute kidney injury (AKI) prediction or reclassification power according to the three eGFR equations. We performed a retrospective observational study within a tertiary hospital from 2011 to 2021. Acute kidney injury was defined according to KDIGO serum creatinine criteria. Glomerular filtration rate estimates were calculated by three GFR estimating equations: 2009 and 2021 CKD-EPIcr, and EKFC. In three equations, AKI prediction performance was evaluated with area under receiver operator curves (AUROC) and reclassification power was evaluated with net reclassification improvement analysis. A total of 187,139 individuals, including 27,447 (14.7%) AKI and 159,692 (85.3%) controls, were enrolled. In the multivariable regression prediction model, the 2009 CKD-EPIcr model (continuous eGFR model 2, 0.7583 [0.755-0.7617]) showed superior performance in AKI prediction to the 2021 CKD-EPIcr (0.7564 [0.7531-0.7597], < 0.001) or EKFC model in AUROC (0.7577 [0.7543-0.761], < 0.001). Moreover, in reclassification of AKI, the 2021 CKD-EPIcr and EKFC models showed a worse classification performance than the 2009 CKD-EPIcr model. (-7.24 [-8.21--6.21], -2.38 [-2.72--1.97]). Regarding AKI risk stratification, the 2009 CKD-EPIcr equation showed better discriminative performance compared to the 2021 CKD-EPIcr equationin the study population.

Performance evaluation of Chronic Kidney Disease Epidemiology Collaboration equations for estimated glomerular filtration rate compared to inulin clearance in Koreans.

A race-free glomerular filtration rate (GFR) estimation equation has recently been developed. However, the performance of the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations needs to be evaluated in Asian populations. We performed a cross-sectional study at a single center in South Korea. The measured GFR (mGFR) was determined based on systemic inulin clearance. The GFR was estimated using the five CKD-EPI equations: 2009 CKD-EPIcr, 2012 CKD-EPIcr-cys, 2012 CKD-EPIcys, 2021 CKD-EPIcr, and 2021 CKD-EPIcr-cys. The performances of five estimated GFR (eGFR) equations were assessed by bias, precision, and accuracy (percentage of estimates within 30% of mGFR). The median mGFR and interquartile range (IQR) was 53.5 (32.4-80.0) mL/min/1.73 m2. The mGFR better correlated with 2009 CKD-EPIcr (ρ = 0.628) and 2021 CKD-EPIcr-cys (ρ = 0.806) than with 2021 CKD-EPIcr (ρ = 0.623) and 2012 CKD-EPIcr-cys (ρ = 0.801). The median bias of 2009 CKD-EPIcr and 2012 CKD-EPIcr-cys were lower than those of 2021 CKD-EPI equations (2009 CKD-EPIcr, 2.24 [IQR, -8.83 to 17.39] vs. 2021 CKD-EPIcr, 5.40 [IQR, -6.04 to 20.40]; 2012 CKD-EPIcr-cys, 6.74 [IQR, -2.81 to 20.80] vs. 2021 CKD-EPIcr-cys, 10.54 [IQR, 0.30-24.37]; all in mL/min/1.73 m2). The percentage of eGFR values within 30% of mGFR was higher in 2009 CKD-EPIcr and 2012 CKD-EPIcr-cys equations than 2021 CKD-EPI equations. The CKD prevalence in 2009 CKD-EPIcr, 2021 CKD-EPIcr, 2012 CKD-EPIcr-cys, and 2021 CKD-EPIcr-cys was 54.8%, 51.0%, 47.7%, and 44.8%, respectively. Our study demonstrated better performance of the original CKD-EPIcr and CKD-EPIcr-cys equations than the 2021 new CKD-EPI equations. We do not recommend the adoption of the new CKD-EPI equations in Korea.

How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.

Mechanisms underlying kidney benefits with sodium-glucose cotransporter-2 (SGLT2) inhibition in heart failure and/or type 2 diabetes (T2D) with established cardiovascular disease are currently unclear. We evaluated post hoc the factors mediating the effect of empagliflozin on a composite kidney outcome (first sustained estimate glomerular filtration rate ≥40% reduction from baseline, initiation of renal replacement therapy, or death due to kidney disease) in EMPA-REG OUTCOME. Variables, calculated as change from baseline or updated mean, were evaluated as time-dependent covariates and using a landmark approach (at Week 12) in Cox regression analyses. In multivariable analyses, variables with the greatest mediating effect were added using a step-up procedure. In univariable time-dependent updated mean covariate analyses, the strongest mediator was hematocrit (99.5% mediation). Hemoglobin, uric acid, and urine albumin-to-creatinine ratio mediated 79.4%, 33.2%, and 31.0%, respectively. Multivariable analyses were not performed due to the very strong mediation effect of hematocrit. In univariable Week 12 landmark change from baseline analyses, the strongest mediators included hematocrit (40.7%), glycated hemoglobin (28.3%), systolic blood pressure (16.8%), and free fatty acids (16.5%), which yielded a combined mediation of 78.9% in multivariable analysis. Changes in hematocrit and hemoglobin were the strongest mediators of empagliflozin's kidney benefits in EMPA-REG OUTCOME participants with T2D and cardiovascular disease.

Effect of Intravitreal Anti-Endothelial Growth Factor Agents on Renal Function in Patients With Diabetes Mellitus

BackgroundIntravitreal administration of vascular endothelial growth factor inhibitors (anti-VEGF) is the treatment of choice in retinal pathology associated with type 2 diabetes mellitus (DM2). We aimed to analyze the effect on renal function in patients with DM2 after intravitreal anti-VEGF administration. MethodsSingle-center retrospective and observational study of patients with DM2 with and without chronic kidney disease (CKD). We analyzed the evolution of renal function after anti-VEGF onset, compared with a control group. ResultsWe included 45 patients (55.6% male) who received anti-VEGF therapy. Mean age was 74.4±11.5 (50-91) years. These were compared with 45 patients with similar characteristics. After 12-months, 76.3% had CKD with a mean reduction in estimate glomerular filtration rate (eGFR) of 19.4%. Nine patients (20%) had a >25% reduction in eGFR, and three patients (6.7%) had a >50% reduction in GFR. At 24-months, 80% of patients had CKD with a mean eGFR drop of 28%. The mean eGRF slope of patients who had received anti-VEGF treatment was 10 ml/min/year compared to 1,5 ml/min/year in the control group (p<0.05). After the first administration, five patients (17.2%) in the CKD group required renal replacement therapy during follow-up (mean time 22±12 months). Main risk factors for need of dialysis were age, presence of previous CKD, and baseline proteinuria. ConclusionIntravitreal anti-VEGF administration is a risk factor for CKD and rapid progression to end-stage kidney disease in patients with previous CKD. Knowing these drugs' implications is crucial to avoid CKD progression and opportunely limit their use in certain patients.