Mean mGFR Research Articles

Evaluation of Race-Neutral Glomerular Filtration Rate Estimating Equations in an Indian Population

Glomerular filtration rate (GFR) estimation equations have not been extensively validated in the Indian population. Preliminary data showed that the widely used creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr) 2009 significantly overestimated GFR in Indians. Newer estimated GFR (eGFR) equations based on creatinine and cystatin C, omitting the race, have been recently proposed. We investigated the performance of race-free eGFR equations in the Indian population. Patients with chronic kidney disease (CKD) and potential kidney donors attending the outpatient clinic at the Postgraduate Institute of Medical Education and Research Chandigarh, India, were screened for enrolment. GFR was measured by urinary clearance of inulin and plasma clearance of iohexol. Performance of eGFR equations (CKD-EPICr(2021), CKD-EPICr-Cys(2021), CKD-EPICr(2009), CKD-EPICr-Cys(2012), CKD-EPICys, 2020Csy-B2M-BTP and 2020Cr-Csy-B2M-BTP, EKFCcr, EKFCcys, and EKFCcr-cys) were assessed against measured GFR (mGFR) using bias, precision, and accuracy (root mean square error [RMSE], mean absolute error [MAE] and P30 [% with eGFR within 30% of mGFR]). A total of 412 subjects (55% with CKD), average age 47 ± 11 years with an equal distribution of males and females were enrolled. The mean mGFR in the study population was 54.2 ± 30.2 ml/min per 1.73 m2. The average mGFR in the potential kidney donor's subgroup was 79.5 ± 23.2 ml/min per 1.73 m2. Bias was highest for creatinine-based eGFR equations (CKD-EPIcr(2021):-19.2 [-21.3 to-17.0] ml/min per 1.73 m2and CKD-EPIcr(2009):-17.0 [-19.1 to-15.0] ml/min per 1.73 m2). Cystatin C- (either alone or with other markers) based equations were slightly better but still did not reach P30≥ 80%. Race-neutral CKD-EPICr(2021) equation did not significantly improve performance as compared to CKD-EPICr(2009) equation. These observations emphasize the need for developing new eGFR equations for Indians and to standardize the mGFR for easy access to care providers for individualized patient care.

Pegloticase-Induced Rapid Uric Acid Lowering and Kidney and Cardiac Health Markers in Youth-Onset Type 2 Diabetes: A Pilot Clinical Trial

Rationale & ObjectiveElevated serum uric acid (SUA) is a risk factor for incident hypertension and diabetic kidney disease in young persons with type 2 diabetes (T2D), particularly men. The acute benefit of aggressively lowering SUA on kidney and cardiovascular function in this population remains underexplored. This study was conducted to investigate the impact of a single pegloticase infusion on kidney and cardiovascular function. Study DesignAn open-label pilot trial. Setting & ParticipantsThe study involved 10 young adult males with youth-onset T2D and SUA levels ≥5 mg/dL. Intervention(s)Participants received a single infusion of pegloticase (8 mg). Evaluations were conducted using iohexol-based measured glomerular filtration rate (mGFR) and cardiac/kidney MRI before and one week after infusion. OutcomesThe primary outcomes were changes in SUA and mGFR one week after pegloticase infusion. ResultsNine participants (mean [±SD] age 22±5 years, HbA1c 8.6±3.3%, BMI 40.1±11.0 kg/m2, SUA 6.7±1.1 mg/dL) completed the pegloticase infusion and were included in the analysis. One week after the infusion, median [p25,p75] SUA concentrations dropped from 6.4 [5.6,7.6] to 0.5 [0.5,4.6] mg/dL (p=0.01). Mean mGFR increased from 113±20 to 122±19 ml/min per 1.73 m2 (p=0.004). Among responders (SUA reduction ≥3 mg/dL), an increase in mGFR correlated with an increase in renal artery blood flow (r:0.60, p=0.24) and decrease in SUA (r:-0.79, p=0.05). Mean MRI peak longitudinal cardiac strain additionally decreased from 15.4±2.2 to 13.1±2.2 % (p=0.03) in these responders. LimitationsThe pilot nature of the study and the small sample size limit the generalizability of the findings. ConclusionsIn young adult males with T2D, a single pegloticase infusion decreased SUA levels, which increased mGFR and was strongly associated with increased renal blood flow and impaired cardiac global longitudinal strain. Further research is required to assess the long-term efficacy and safety of pegloticase in patients with T2D.

Diabetic status and the performances of creatinine- and cystatin C-based eGFR equations.

The estimation of glomerular filtration rate (GFR) is one main tool to detect renal disease. The most used biomarker remains serum creatinine and the European Kidney Function Consortium (EKFCcrea) equation is the most validated in Europe. More recently, cystatin C, has been proposed. We studied the performances of the EKFC equations in a large cohort of subjects according to their diabetic status. Four cohorts from the EKFC dataset were retrospectively considered in which the diabetic status was available. GFR was measured by plasma clearances (mGFR) (iohexol or 51Cr-EDTA). The performance of the equations was assessed by calculating bias, precision (IQR) and P30 (percentage of eGFR-values within±30% of mGFR). In the whole population (n=6158), median [IQR] age was 61 [47;72] years, with 45.8% women. Mean mGFR was 60 [39;82] mL/min/1.73m². Compared to non-diabetic individuals (n=5124), diabetic patients (n=1034) were older, more frequently male, heavier, and had lower mGFR. The performance of the EKFCcys equation was similar to EKFCcrea, but the EKFCcrea+cys had better P30 than the single-biomarker equations. P30 values were substantially lower in diabetic patients than in non-diabetic but, according to a matched analysis, this is mainly explained by the difference in GFR levels between the two populations, not by diabetic status. We showed that equation combining creatinine and cystatin C present a better performance. If accuracy of equations seems better in non-diabetic than in diabetic individuals, it is more due to differences in GFR levels than to the diabetic status.

Is race adjustment necessary to estimate glomerular filtration rate in South Brazilians?

Race coefficients (RC) in equations to estimate glomerular filtration rate (GFR) have been highly questioned. We aimed to evaluate the performance of three equations, namely 2009 Chronic Kidney Disease Epidemiology Collaboration (2009 CKD-EPI), 2021 CKD-EPI, and European Kidney Function Consortium (EKFC) in self-reported Black and White Brazilians. Our cross-sectional study compared estimated GFR (eGFR) with 51Cr-EDTA measured GFR (mGFR) in healthy adults, patients with type 2 diabetes mellitus with or without chronic kidney disease (CKD), and in non-diabetic individuals with CKD. The performance of these equations was assessed using Bland-Altman plots, Lin's concordance correlation coefficient (CCC), bias, P30, and P15 accuracy. Three hundred six White adults (aged 53 ± 17 years, 55% women, mean mGFR: 83 ± 32 mL/min/1.73m2) and 48 Black participants (aged 53 ± 17 years, 58% women, mGFR: 90 ± 34 mL/min/1.73m2) were included. No equation achieved the desirable P30 accuracy value of 90%, neither in White (2009 CKD-EPI:78%, 2021 CKD-EPI:76% and EKFC:77%, p = 0.368) nor in Black volunteers (respective values of 77%, 75%, and 77%; p = 0.882). The 2009 CKD-EPI showed the best performance in Black participants (bias: 4.04; CCC: 0.848), whereas the 2021 CKD-EPI performed better in Whites, with smaller bias (1.45), and better concordance correlation coefficient (0.790). The EKFC presented the worst performance. All equations underdiagnosed advanced CKD in White participants, but not in Black. The 2021 CKD-EPI does not outperform the 2009 CKD-EPI. Instead, it underestimated the occurrence of CKD in White participants. Thus, we do not recommend replacing the 2009 with the new 2021 CKD-EPI in the Brazilian population.

Assessing bias in GFR estimating equations: improper GFR stratification can yield misleading results.

Assessing bias (estimated - measured) is key to evaluating glomerular filtration rate (GFR). Stratification by subgroups can indicate where equations perform differently. However, there is a fallacy in the assessment of two instruments (e.g., eGFR and mGFR) when stratifying on the level of only one of those instruments. Here, we present statistical aspects of the problem and a solution for GFR stratification along with an empirical investigation using data from the CKiD study. Compared and contrasted biases (eGFR relative to mGFR) with 95% confidence intervals within strata of mGFR only, eGFR only, and the average of mGFR and eGFR using data from the Chronic Kidney Disease in Children (CKiD) study. A total of 304 participants contributed 843 GFR studies with a mean mGFR of 48.46 (SD = 22.72) and mean eGFR of 48.67 (SD = 22.32) and correlation of 0.904. Despite strong agreement, eGFR significantly overestimated mGFR when mGFR < 30 (+ 6.2%; 95%CI + 2.9%, + 9.7%) and significantly underestimated when mGFR > 90 (-12.2%; 95%CI - 17.3%, - 7.0%). Significant biases in opposite direction were present when stratifying by eGFR only. In contrast, when stratifying by the average of eGFR and mGFR, biases were not significant (+ 1.3% and - 1.0%, respectively) congruent with strong agreement. Stratifying by either mGFR or eGFR only to assess eGFR biases is ubiquitous but can lead to inappropriate inference due to intrinsic statistical issues that we characterize and empirically illustrate using data from the CKiD study. Using the average of eGFR and mGFR is recommended for valid inferences in evaluations of eGFR biases.

External Validation of a Novel Multimarker GFR Estimating Equation.

Using multiple markers may improve accuracy in glomerular filtration rate (GFR) estimation. We sought to externally validate and compare the performance a novel multi-marker estimated GFR (panel eGFR) among Black and White persons using the Genetic Epidemiology Network of Arteriopathy cohort. 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-EPI 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. In the overall cohort, 49% were Black individuals and mean mGFR was 79 ml/min/1.73m2. Panel eGFR overestimated mGFR (bias: -2.4 ml/min/1.73m2; 95% confidence interval [CI]: -4.4, -0.7), eGFR-Cr-CysC underestimated mGFR (bias: 4.8 ml/min/1.73m2; 95% CI: 2.1, 6.7), while eGFR-Cr was unbiased (bias: 2.0 ml/min/1.73m2; 95% CI: -1.1, 4.6). All equations had comparable accuracy. Among Black males age <65 years, both eGFR-Cr (bias: 17.0 ml/min/1.73m2; 95% CI: 8.6, 23.5) and eGFR-Cr-CysC (bias: 14.5 ml/min/1.73m2; 95% CI: 6.0, 19.7) underestimated mGFR whereas panel eGFR was unbiased (bias: 1.7 ml/min/1.73m2; 95% CI: -3.4, 10.0). Metrics of accuracy for all eGFRs were acceptable in all subgroups except for panel eGFR in Black females <65 years (P30: 73.3%). Panel eGFR can be used to estimate mGFR and may have utility among Black males age <65 years where current CKD-EPI equations are biased.

CKD-EPI and EKFC GFR Estimating Equations: Performance and Other Considerations for Selecting Equations for Implementation in Adults.

New eGFR equations from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) using creatinine (eGFRcr), cystatin C (eGFRcys), and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice, leading to uncertainty in selecting equations for implementation. The authors evaluated performance of equations in an independent population of 4050 adults and evaluated other considerations important for implementation. They found that CKD-EPI and EKFC equations are approaching convergence, with better performance of eGFRcr-cys equations in the overall group and fewer differences among race, sex, and age subgroups than eGFRcr equations. Larger differences among eGFRcr equations reflect regional population differences in creatinine, forcing a trade-off between accuracy and uniformity in global implementation of eGFRcr equations. More widespread use of cystatin C could avoid this trade-off. New CKD-EPI and EKFC eGFR equations using eGFRcr, eGFRcys, and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice. A better understanding of the equations, including their performance in race, sex and age subgroups, is important for selection of eGFR equations for global implementation. We evaluated performance (bias and P 30 ) of equations and methods used for equation development in an independent study population comprising 4050 adults pooled from 12 studies. The mean (SD) measured GFR was 76.4 (29.6) ml/min per 1.73 m 2 and age 57.0 (17.4) years, with 1557 (38%) women and 579 (14%) Black participants. Coefficients for creatinine, cystatin C, age, and sex in the CKD-EPI and EKFC equations are similar. Performance of the eGFRcr-cys equations in the overall population (bias <±5 ml/min per 1.73 m 2 and P 30 >90%) was better than the eGFRcr or eGFRcys equations, with fewer differences among race, sex, and age subgroups. Differences in performance across subgroups reflected differences in diversity of source populations and use of variables for race and sex for equation development. Larger differences among eGFRcr equations reflected regional population differences in non-GFR determinants of creatinine. CKD-EPI and EKFC equations are approaching convergence. It is not possible to maximize both accuracy and uniformity in selecting one of the currently available eGFRcr equations for implementation across regions. Decisions should consider methods for equation development in addition to performance. Wider use of cystatin C with creatinine could maximize both accuracy and uniformity of GFR estimation using currently available equations.

Alteration of the maximal renal water excretion capacity with kidney function and age in human.

The kidney's capability to concentrate and dilute urine is crucial to maintaining body fluid compartments and plasma osmolality. Advanced age and chronic kidney disease (CKD) result in decreased maximal urine concentration. Less is known regarding urine dilution ability. The primary purpose of this study was to determine the relationship between maximal renal water excretion and renal function, age, and gender in humans. This monocentric retrospective study includes patients referred to the Department of Clinical Physiology in Toulouse University Hospital to measure the glomerular filtration rate (mGFR) between April 2013 and February 2018. mGFR was assessed using inulin renal clearance and required ample hydration. We quantified the effects of age, gender and mGFR have on water excretion ability, which was assessed by minimal urinary osmolality (minUosm) and maximal free water clearance (maxCH2O). 666 patients were included (mean age 51 ± 14years, 53% female). Mean mGFR was 82 ± 25mL/min/1.73m2. MinUosm after hydration was higher in patients with renal insufficiency while maxCH2O was markedly lower. Age was also, with a weaker effect, associated with decreased in water excretion, independently of mGFR. MaxCH2O clearance was similar in both genders, whereas minUosm was lower in women, possibly resulting from a lower osmotic load. This study shows a decrease in maximal urinary dilution capacity and free water clearance with CKD and age, without gender difference. These alterations are mild but must be considered when a significant water intake is required or in the case of hyponatremia.

Additive effects of dapagliflozin and finerenone on albuminuria in non-diabetic CKD: an open-label randomized clinical trial.

Dapagliflozin and finerenone reduce albuminuria and slow CKD progression, but additive effects remain unstudied. We compared their individual and combined efficacy and safety in patients with non-diabetic CKD. In an open-label, randomized clinical trial, we included patients aged 18-80 on maximal tolerated ACE inhibitor or angiotensin receptor blocker with eGFR 25-45mL/min/1,73m2 and albuminuria 150-2000mg/g. Participants received either finerenone 20mg/day or dapagliflozin 10mg/day for four weeks, followed by combination therapy for four weeks. Data were collected at baseline, 4 and 8 weeks. Twenty patients (10 per group) with a mean mGFR of 34mL/min/1,73 m2 and a mean urine albumin creatinine ratio (UACR) of 469mg/g were included. Finerenone alone or in addition to dapagliflozin resulted in -24% (95% CI, -36% to -11%) and -34% (95% CI, -47% to -18%) change in UACR, respectively. Dapagliflozin alone or in addition to finerenone resulted in -8% (95% CI, -22 to 9%) and -10% (95% CI, -28% to 12%) change in UACR, respectively. Overall, UACR change after 8 weeks was -36% (95% CI, -46% to -24%). After 8 weeks, systolic blood pressure and mGFR were reduced by 10mmHg (95% CI, 6-13mmHg) and 7mL/min/1,73 m2 (95% CI, 5-8mL/min/1,73 m2). Adverse effects were minimal. The combination of finerenone and dapagliflozin was safe and significantly reduced albuminuria. The effect of combination therapy was at least equal to the calculated, combined effect of each of the drugs, suggesting an additive effect on albuminuria. Larger studies assessing long-term effects and safety are warranted.

Estimated glomerular filtration rate calculated by serum creatinine lacks precision and accuracy in adults with type 2 diabetes with preserved renal function

AimsWe evaluated the performance of creatinine-based equations that are currently used to estimate glomerular filtration rate (GFR) in people with type 2 diabetes compared to measured GFR using gold-standard methods. MethodsIn this post-hoc analysis, 32 participants underwent repeated measurement of GFR by inulin clearance (mGFR). GFR was estimated by serum creatinine using the MDRD (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI) equations four times over the course of one month. Performance was evaluated using measurements of bias (mean difference), precision (SD), and inaccuracy (proportion of eGFR that differed by >20 % of mGFR). Treatment and time effects on bias were evaluated using linear mixed effects models. ResultsAt baseline, participants (38 % female) were age 60 ± 8 years, had diabetes duration of 9 ± 7 years, HbA1c 56 ± 9 mmol/mol (7.2 ± 0.8 %), and BMI 31.0 ± 6.2 kg/m2. Mean mGFR was 113 ± 24, mean eGFRMDRD was 93 ± 12, and mean eGFRCKD-EPI was 94 ± 9 mL/min/1.73 m2. When 128 observations (32 participants measured 4 times) were evaluated, both equations substantially underestimated mGFR. For eGFRMDRD, mean bias was −21.5 mL/min/1.73 m2, precision was 22.7 mL/min/1.73 m2, and 46 % of observations differed by >20 %. Results were similar for eGFRCKD-EPI. No time or treatment effects on bias were observed. ConclusionsIn adults with type 2 diabetes and preserved renal function, eGFR equations underestimated mGFR, lacked precision and accuracy, and performance was lower at higher ranges of mGFR. Current eGFR equations by serum creatinine are inaccurate in adults with type 2 diabetes with preserved renal function, highlighting the necessity to develop new methods to measure kidney function at earlier stages of diabetic kidney disease.

#4506 ACCURACY OF NOVEL GFR ESTIMATING EQUATIONS BASED ON CREATININE, CYSTATIN C OR BOTH IN ROUTINE CARE

Abstract Background and Aims New equations to estimate GFR (eGFR) based on creatinine, cystatin C or both have been developed in the last two years. A comprehensive comparison of their accuracy is currently lacking, particularly in cohorts not involved in their development or validation and among people with comorbid conditions. Method We included 6174 adults from the Stockholm Creatinine Measurements (SCREAM) project referred for plasma clearance of iohexol during 2011-2021, in whom we observed 9579 concurrent measurements of creatinine, cystatin C and iohexol clearance. We assessed the performance against measured GFR (mGFR) of eGFR equations proposed by the CKD-EPI collaboration (CKD-EPI 2009, 2012 and 2021), European Kidney Function Consortium (EKFC 2021 and 2023), and the revised Lund-Malmö (2011) and CAPA (2014) equations, which are used in Sweden. Bias was expressed as the median difference in eGFR minus mGFR, with negative biases indicating underestimation of mGFR. P30 described the percentage of individuals with eGFR within 30% of mGFR. Correct classification was defined as agreement of eGFR and mGFR categories using the KDIGO GFR categories. Subgroup analyses were conducted according to age, sex, BMI, eGFR, cancer, cardiovascular disease, diabetes, heart failure and liver disease. Results Mean age was 57 years, 46% of participants were female, mean mGFR was 62 mL/min/1.73 m2 and mean BMI was 26 kg/m2. Cardiovascular disease was the most common comorbid condition (30%), followed by liver disease (28%), diabetes (26%) and cancer (26%). Equations that used both creatinine and cystatin C had better performance than eGFR using each marker alone, regardless of the equation used; all such equations had small bias and P30 close to 90%. Among creatinine-based equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger overestimates of mGFR than EKFC 2021 and revised Lund-Malmö, with median biases of 5.6, 9.1, 2.7 and 0.2 mL/min/1.73 m2, respectively (Table 1). There were no meaningful differences in performance across eGFR equations based on cystatin C. Findings were consistent across subgroup analyses stratifying for comorbid conditions (Figure 1). Conclusion eGFR equations that combined information on creatinine and cystatin C performed better than equations based on creatinine or cystatin C alone in this Swedish cohort of routine referrals for plasma clearance of iohexol. There was larger variation in the performance of equations based on creatinine than cystatin C.

#3125 EXTERNAL VALIDATION OF A NOVEL MULTIMARKER GFR ESTIMATING EQUATION

Abstract Background and Aims The use of multiple markers may improve the accuracy in glomerular filtration rate (GFR) estimation especially when the interpretation of creatinine and cystatin C is limited. We sought to externally validate a recently developed multi-marker nuclear magnetic resonance (NMR)-based estimated GFR equation (eGFR-NMR) using the biracial Genetic Epidemiology Network of Arteriopathy cohort. Method We included 224 sex, race/ethnicity, and mGFR-category-matched participants. GFR was measured using urinary clearance of iothalamate (mGFR). We calculated eGFR-NMR using serum creatinine, valine, myo-inositol, and cystatin C, age, and sex. We compared the reliability of eGFR-NMR with current eGFR equations (2021 Chronic Kidney Disease Epidemiology Collaboration equations for creatinine [eGFR-Cr] and creatinine with cystatin C [eGFR-Cr-CysC]) using median bias, precision, and accuracy metrics. In particular, we evaluated its performance in age, sex, and race subgroups. Results In the overall cohort, mean age was 63 (±8) years, 54% were females, 49% were Black individuals, and mean mGFR was 78.7 (±24.3) ml/min/1.73 m2. eGFR-NMR overestimated mGFR by 2 mL/min/1.73 m2 (95% CI, 4 to 0.7) while eGFR-Cr-CysC underestimated mGFR by −5 mL/min/1.73 m2 (95% CI, −2 to −7). All equations had acceptable accuracy metrics. When stratified by age, sex, and race, eGFR-NMR performed the best among Black males age &amp;lt;65 years compared to current equations (Figure 1). In this subgroup, eGFR-NMR was unbiased (bias, 2mL/min/1.73 m2 [95% CI, -3 to 10]) compared to substantial biases of eGFR-Cr (bias, 17 mL/min/1.73 m2 [95% CI, 9 to 24]) and eGFR-Cr-CysC (bias, 15 mL/min/1.73 m2 [95% CI, 6 to 20]). In other subgroups, measures of accuracy for eGFR-NMR, eGFR-Cr, eGFR-Cr-CysC were generally similar. Conclusion eGFR-NMR can be used to estimate mGFR and was more accurate than CKD-EPI equations among Black males age &amp;lt;65 years.

Estimated GFR Accuracy When Cystatin C– and Creatinine-Based Estimates Are Discrepant in Older Adults

Serum creatinine and cystatin C are used to estimate glomerular filtration rate, but creatinine-based estimated glomerular filtration rate (eGFRcr), cystatin C-based estimated glomerular filtration rate (eGFRcys), and combined creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) are often divergent, particularly in older adults. We investigated which estimated glomerular filtration rate (eGFR) was more accurate and less biased compared with measured glomerular filtration rate (mGFR). A diagnostic test study from the Berlin Initiative Study. The study population included 657 individuals aged 70 years or older with iohexol plasma clearance (mGFR) and serum creatinine and cystatin C measurements: 567 community-dwelling participants and 90 with a serum creatinine of≥1.5 mg/dL. We defined 3 groups on the basis of the difference eGFRcys-eGFRcr: whether< -5 mL/min/1.73 m2 (lower eGFRcys), within 5 mL/min/1.73 m2 (reference), or≥ 5 mL/min/1.73 m2 (lower eGFRcr). eGFRcr, eGFRcys, and eGFRcr-cys were compared to mGFR to assess bias and accuracy. Median bias (eGFR minus mGFR) with 95% CIs and accuracy (percentage of eGFR values within±30% of mGFR). The mean±standard deviation age was 78±6 years; the mean eGFRcys, eGFRcr, and eGFRcr-cys were 59±23, 64±20, and 61±22 mL/min/1.73 m2, respectively, and the mean mGFR was 56±19 mL/min. Half of the participants were in the lower eGFRcys group (n=337, 51%). Among them, the median bias for eGFRcys was the lowest (median bias,-2.7; 95% CI,-3.8 to-1.9) compared with the other eGFR equations. Conversely, in the lower eGFRcr group (n=121, 18%), the median bias for eGFRcr was the lowest compared with those for eGFRcys and eGFRcr-cys (2.9; [95% CI, 0.9-4.8] vs 13.8 [95% CI, 11.4-15.6] and 9.5 [95% CI, 7.7-11.0], respectively). Accuracy (percentage of eGFR values within±30% of mGFR) was 93% for eGFRcr in the lower eGFRcr group and 92% for eGFRcys and 94% for eGFRcr-cys in the lower eGFRcys group. Untested generalizability in younger populations. Among older adults, the lower eGFR between eGFRcys and eGFRcr was a more accurate and less biased estimate of mGFR when comparing the groups.

Comparing Estimated and Measured Glomerular Filtration Rate in Children with Posterior Urethral Valve.

Posterior urethral valve (PUV) is obstructive uropathy that may lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD) in children. Glomerular filtration rate (GFR) measurement remains the gold standard for renal function measurement. However, due to its less availability and cumbersome, it is not commonly used, and GFR is estimated utilizing various endogenous filtration markers. This study includes pediatric patients with PUV. We aimed to compare the measured GFR (mGFR) with various creatinine-based estimated GFR methods (eGFR). A single-center retrospective study included 62 treated cases of PUV, postvalve fulguration. The mGFR measured by 99mTc-diethylenetriaminepentaacetate in vitro method and compared with eight eGFR (Schwartz, Cockcroft-Gault [CG], Counahan-Barratt [CB], CKD Epidemiology Collaboration [CKD-EPI], full-age spectrum [FAS] age, FAS height (FAS Ht), Schwartz-Lyon [SL], and Ht independent). Patients were subdivided into different CKD grades and compared with various eGFR. PUV is a common cause of CKD in children and needs special consideration as there is growth retardation associated with it. It decreases creatinine production and thus fallacies in eGFR measurement. There is a requisite to identify and closely monitor the subset of patients with baseline decreased renal function and therefore at risk of developing ESRD. A total of 62 patients were included. Mean age and serum creatinine levels were 8.02 ± 5.53 years and 1.15 ± 0.95 mg/dl (range: 0.4-4.5), respectively. The mean mGFR was 61.6 ± 31.80 mL/min/1.73 m2 and a positive variable correlation was 0.46-0.77 between mGFR and eGFR. Based on mGFR, there were 14 (22.6%), 21 (33.8%), 13 (20.9%), 9 (14.5%), and 5 (8.1%) patients in Grades I-V, respectively. The correct classification of the CKD grades was noted in 25 (40.3%), 16 (25.8%), 32 (51.6%), 16 (25.8%), 25 (40.3%), 27 (43.5%), 26 (41.9%), and 28 (45.2%) patients by Schwartz, CG, CB, CKD-EPI, FAS age, FAS Ht, SL, and Ht-independent equation. The eGFR overestimates GFR at the lower level and underestimates at higher levels. Our results confirm the considerable limitations of various creatinine-based clearance methods for estimating actual GFR. The creatinine clearance-based eGFR should not replace the measurement of the GFR. An initial measure of the mGFR followed by serial follow-up with the eGFR equation may be done. The most accurate eGFR equations are CB for Grade II, SL or Ht independent for Grade III, FAS age for Grade IV, and SL for Grade V CKD.

Integrated proteomic and metabolomic modules identified as biomarkers of mortality in the Atherosclerosis Risk in Communities study and the African American Study of Kidney Disease and Hypertension

BackgroundProteins and metabolites are essential for many biological functions and often linked through enzymatic or transport reactions. Individual molecules have been associated with all-cause mortality. Many of these are correlated and might jointly represent pathways or endophenotypes involved in diseases.ResultsWe present an integrated analysis of proteomics and metabolomics via a local dimensionality reduction clustering method. We identified 224 modules of correlated proteins and metabolites in the Atherosclerosis Risk in Communities (ARIC) study, a general population cohort of older adults (N = 4046, mean age 75.7, mean eGFR 65). Many of the modules displayed strong cross-sectional associations with demographic and clinical characteristics. In comprehensively adjusted analyses, including fasting plasma glucose, history of cardiovascular disease, systolic blood pressure and kidney function among others, 60 modules were associated with mortality. We transferred the network structure to the African American Study of Kidney Disease and Hypertension (AASK) (N = 694, mean age 54.5, mean mGFR 46) and identified mortality associated modules relevant in this disease specific cohort. The four mortality modules relevant in both the general population and CKD were all a combination of proteins and metabolites and were related to diabetes / insulin secretion, cardiovascular disease and kidney function. Key components of these modules included N-terminal (NT)-pro hormone BNP (NT-proBNP), Sushi, Von Willebrand Factor Type A, EGF And Pentraxin (SVEP1), and several kallikrein proteases.ConclusionThrough integrated biomarkers of the proteome and metabolome we identified functions of (patho-) physiologic importance related to diabetes, cardiovascular disease and kidney function.

Renal function after liver transplantation: Real-world experience with basiliximab induction and delayed reduced-dose tacrolimus.

Routine use of delayed reduced-dose calcineurin-inhibitor treatment with induction immunosuppression in liver transplantation to minimize post-operative kidney injury is still scarce. To evaluate real-world experience of basiliximab induction with delayed reduced-dose tacrolimus. In a retrospective cohort study, kidney function was evaluated pre- and postoperatively by measured glomerular filtration rate (mGFR). Adult patients undergoing liver transplantation between 2000 and 2017 were divided into a conventional treatment group (immediate-introduction of tacrolimus, target trough levels 10-15ng/mL, and corticosteroids, n=203) and a revised treatment group (basiliximab induction, reduced-dose tacrolimus, target through levels 5-8ng/mL, delayed until day three, and mycophenolate mofetil 2000mg/day, n=343). Mean mGFR was similar between groups at wait-listing (85.3vs 84.1ml/min/1.73m², p=0.60), but higher in the revised treatment group at 3 (56.8vs 63.4ml/min/1.73m², p=0.004) and 12 months post-transplant (60.9vs 69.7ml/min/1.73m², p<0.001); this difference remained after correcting for multiple confounders and was independent of pre-transplant mGFR. In the revised treatment group, biopsy proven acute rejection rate was lower (38% vs. 21%, p<0.001), and graft-survival better (p=0.01). Basiliximab induction with delayed reduced-dose tacrolimus is associated with less kidney injury when compared to standard-dose tacrolimus, without increased risk of rejection, graft loss or death.

Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation : A Cross-Sectional Study.

Although the population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate (mGFR) are well recognized, the magnitude and potential clinical implications of individual-level differences are unknown. To quantify the magnitude and consequences of the individual-level differences between mGFRs and eGFRs. Cross-sectional study. Four U.S. community-based epidemiologic cohort studies with mGFR. 3223 participants in 4 studies. The GFRs were measured using urinary iothalamate and plasma iohexol clearance; the eGFR was calculated from serum creatinine concentration alone (eGFRCR) and with cystatin C. All GFR results are presented as mL/min/1.73 m2. The participants' mean age was 59 years; 32% were Black, 55% were women, and the mean mGFR was 68. The population-level differences between mGFR and eGFRCR were small; the median difference (mGFR-eGFR) was -0.6 (95% CI, -1.2 to -0.2); however, the individual-level differences were large. At an eGFRCR of 60, 50% of mGFRs ranged from 52 to 67, 80% from 45 to 76, and 95% from 36 to 87. At an eGFRCR of 30, 50% of mGFRs ranged from 27 to 38, 80% from 23 to 44, and 95% from 17 to 54. Substantial disagreement in chronic kidney disease staging by mGFR and eGFRCR was present. Among those with eGFRCR of 45 to 59, 36% had mGFR greater than 60 whereas 20% had mGFR less than 45; among those with eGFRCR of 15 to 29, 30% had mGFR greater than 30 and 5% had mGFR less than 15. The eGFR based on cystatin C did not provide substantial improvement. Single measurement of mGFR and serum markers without short-term replicates. A substantial individual-level discrepancy exists between the mGFR and the eGFR. Laboratories reporting eGFR should consider including the extent of this uncertainty to avoid misinterpretation of eGFR as an mGFR replacement. National Institutes of Health.

Accuracy evaluation of 2021 Chronic Kidney Disease Epidemiology Collaboration, Full Age Spectrum and European Kidney Function Consortium equations for estimating glomerular filtration rate in type 2 diabetes mellitus and healthy adults

Background and aimsEstimated glomerular filtration rate (eGFR) equations accuracy has been questioned in diabetes mellitus (DM). We aimed to evaluate the performance of three equations – European Kidney Function Consortium (EKFC), Full Age Spectrum (FAS), and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) – in healthy and type 2 DM participants. Material and methodsThis cross-sectional studycompared eGFR equations withareference method: measured GFR (mGFR) by 51Cr-EDTA. The equations performance was assessed usingBland-Altman plot,concordance correlation coefficient (CCC), bias,P30 andP15 accuracy. ResultsIn the 100 healthy adults included (aged 39 ± 15 years, 67% women, mean mGFR 107 ± 15, 2021 CKD-EPI 109 ± 14, FAS 107 ± 18 and EKFC 101 ± 12 mL/min/1.73 m2), all equations reached P30 accuracy above the desirable benchmark of 90%. In the 122 patients with type 2 DM (aged 61 ± 10 years, 55% women, mGFR97 ± 22, 2021 CKD-EPI 86 ± 20, FAS 83 ± 25 and EKFC 79 ± 18 mL/min/1.73 m2), the equations presented larger biases, worst agreement with mGFR and inferior accuracy, with 2021 CKD-EPI (83%) and EKFC (82%) presenting greater P30 than FAS (77%). ConclusionIn healthy Brazilian adults, 2021 CKD-EPI, FAS and EKFC are suitable to estimate GFR. However, all equations underperform in people with type 2 DM.

Performance of the 2021 CKD-EPI equations without a race coefficient in a multi-racial population of adults with solid tumors: A prospective cross-sectional study.

12064 Background: We previously showed that estimated glomerular filtration rate (eGFR) based on serum creatinine (Scr)(eGFRcr) using the 2009 CKD-EPI equation performed better than Cockroft-Gault equation (CG) in solid tumor patients in Brazil (Onco-GFR Study). In that study, eGFR based on Scr and cystatin C (Scys)(eGFRcr-cys) using the 2012 CKD-EPI was the most accurate equation and suitable for use as a confirmatory test. The CKD-EPI 2009 eGFRcr and 2012 eGFRcr-cys equations include a term for race (Black vs. non-Black). The 2021 CKD-EPI eGFRcr and eGFRcr-cys equations do not include race and are now recommended in the US, but have not been assessed in a multi-racial population or in cancer patients. The aim of this study is to evaluate the performance of the 2021 CKD-EPI equations in the Onco-GFR Study. Methods: Measured GFR (mGFR) was determined using the plasma clearance of 51Cr-EDTA. Scr and Scys assays were traceable to international standards. Results: A group of 1,200 patients recruited between April 2015 and September 2017 were included for analysis. Patients were 58.8±13.2 years, 50.8% male. Race distribution was Black participants 12.8% and non-Black participants 81.2%. Mean (SD) mGFR was 78.5±21.7 ml/min/1.73 m2. For eGFRcr, the overestimation of mGFR was larger for the 2021 vs. 2009 equation -10.0 vs. 8.1 ml/min/1.73m2, resulting in lesser accuracy 1-P30 of 22.3 vs. 19.1, but still more accurate than CG equation (1-P30 of 24.9, P = 0.05). For eGFRcr-cys, the overestimation of mGFR was larger for the 2021 vs. 2012 equation (-4.1 vs. -2.0 ml/min/1.73m2). eGFRcr-cys using the 2021 equation was more accurate than eGFRcr using the 2021 equation and eGFRcys using the 2012 equation (1-P30 9.8 vs. 22.3 and 12.3, p-values &lt; 0.001 and 0.01, respectively) (Table). Conclusions: 2021 CKD-EPI eGFRcr equation race performed better than CG. 2021 CKD-EPI eGFRcr-cys performed better than 2021 eGFRcr and 2012 eGFRcys equations. Removing race from eGFR equations represents an advance and should be incorporated in cancer care. [Table: see text]

MO422: Strong Positive Association Between GFR and the Urine-To-Plasma Urea Concentration Ratio in Patients With Sickle Cell Disease. Possible Functional Meaning

Abstract BACKGROUND AND AIMS Sickle cell disease (SCD) induces a decline in urine concentration and progressive deterioration of kidney (K) function. Hyperfiltration is often observed before this decline, and plasma urea is low. Oral urea or hydroxyurea improves the condition of these patients (pts). These observations draw the attention to renal urea handling in SCD. Studies suggest that addition of urea into the loop of Henle may indirectly modify NaCl concentration at the macula densa and induce a rise in glomerular filtration rate (GFR) by depressing the tubule-glomerular feedback (TGF) [1]. The urine-to-plasma urea concentration ratio (U/P urea) is a novel marker associated with GFR and the progression of disease in ADPKD [2]. The present study addresses the relationship of U/P urea with GFR in SCD pts. METHOD A total of 184 homozygous SCD pts referred to our department were included. They underwent extensive evaluation including measured GFR (mGFR) (51Cr EDTA clearance) and plasma and 24-h urine chemistries. The association between mGFR and U/P urea was tested using univariate, and multivariate stepwise regression analyses. RESULTS Mean age was 35.6 ± 2.8 years (mean ± SD) and body mass index (BMI) 22.2 ± 0.3 kg/m2. Mean mGFR was 107 ± 3 ml/min x 1.73m2. Hyperfiltration was observed in 37% of pts. Urine volume (UV) 1.71 ± 0.75 L/24h. Urea excretion 267 ± 151 mmol/24h. In 13% of pts fractional excretion of urea (FEurea) exceeded 50%. U/P urea (42 ± 20) varied from 6 to 112. It was not associated with 24-h urea excretion but showed a negative association with UV (P &amp;lt; 0.007). mGFR was strongly and positively associated with U/P urea (r = 0.58, P &amp;lt; 0.0001) but not with U/P osmolarity (see Figure and Table). mGFR was also associated with U/P creatinine although more weakly (r = 0.266, p &amp;lt; 0.0001) and with BMI and negatively associated with age, MAP and serum creatinine (creat). After adjustment for U/P creat, the association between mGFR and U/P urea remained highly significant, whereas, after adjustment for U/P urea, the association between mGFR and U/P creat disappeared. In multivariate regression, mGFR remained strongly associated with U/P urea. CONCLUSION Our data show a strong association between mGFR and U/P urea that remains highly significant after multivariate analysis. i) This suggests that a specific estimated GFR equation for SCD patients including the U/P urea ratio could be clinically more relevant than CKD-EPI equations. ii) A specific mechanism may link GFR and intrarenal urea handling, as U/P urea but not U/P osmolarity appears to be involved. Urea could play a role, indirectly, in the regulation of GFR [1]. In SCD, the longer transit time of the blood in vasa recta may favour countercurrent exchanges and lead to a greater addition of urea in loops of Henle (increasing the U/P urea ratio) and thus increasing GFR by reducing TGF. Sickled red cells and resulting in slower blood flow in the medulla may selectively influence urea handling, participating in high FEurea and GFR often observed in SCD pts. iii) As is the case in ADPKD, more attention should be given to longitudinal studies to the relationship between U/P urea and kidney disease progression in SCD pts.